3,861 results on '"HIV Antigens"'
Search Results
2. TCF-1 regulates HIV-specific CD8+ T cell expansion capacity
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Rutishauser, Rachel L, Deguit, Christian Deo T, Hiatt, Joseph, Blaeschke, Franziska, Roth, Theodore L, Wang, Lynn, Raymond, Kyle A, Starke, Carly E, Mudd, Joseph C, Chen, Wenxuan, Smullin, Carolyn P, Matus-Nicodemos, Rodrigo, Hoh, Rebecca, Krone, Melissa R, Hecht, Frederick M, Pilcher, Christopher D, Martin, Jeffrey N, Koup, Richard A, Douek, Daniel C, Brenchley, Jason M, Sékaly, Rafick-Pierre, Pillai, Satish K, Marson, Alexander, Deeks, Steven G, McCune, Joseph M, and Hunt, Peter W
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Sexually Transmitted Infections ,HIV/AIDS ,Infectious Diseases ,Underpinning research ,1.1 Normal biological development and functioning ,Infection ,Good Health and Well Being ,Adult ,Aged ,Animals ,CD8-Positive T-Lymphocytes ,Female ,Gene Knockout Techniques ,HIV Antigens ,HIV Infections ,HIV-1 ,Humans ,Immunologic Memory ,Macaca mulatta ,Male ,Middle Aged ,Simian Acquired Immunodeficiency Syndrome ,Simian Immunodeficiency Virus ,T Cell Transcription Factor 1 ,Viral Load ,Simian immunodeficiency virus ,AIDS/HIV ,Adaptive immunity ,T cells ,Biomedical and clinical sciences ,Health sciences - Abstract
Although many HIV cure strategies seek to expand HIV-specific CD8+ T cells to control the virus, all are likely to fail if cellular exhaustion is not prevented. A loss in stem-like memory properties (i.e., the ability to proliferate and generate secondary effector cells) is a key feature of exhaustion; little is known, however, about how these properties are regulated in human virus-specific CD8+ T cells. We found that virus-specific CD8+ T cells from humans and nonhuman primates naturally controlling HIV/SIV infection express more of the transcription factor TCF-1 than noncontrollers. HIV-specific CD8+ T cell TCF-1 expression correlated with memory marker expression and expansion capacity and declined with antigenic stimulation. CRISPR-Cas9 editing of TCF-1 in human primary T cells demonstrated a direct role in regulating expansion capacity. Collectively, these data suggest that TCF-1 contributes to the regulation of the stem-like memory property of secondary expansion capacity of HIV-specific CD8+ T cells, and they provide a rationale for exploring the enhancement of this pathway in T cell-based therapeutic strategies for HIV.
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- 2021
3. Antigenic competition in CD4+ T cell responses in a randomized, multicenter, double-blind clinical HIV vaccine trial.
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Kallas, Esper, Grunenberg, Nicole, Yu, Chenchen, Manso, Bryce, Pantaleo, Giuseppe, Casapia, Martin, Baden, Lindsey, Valencia, Javier, Sobieszczyk, Magdalena, Van Tieu, Hong, Allen, Mary, Hural, John, Graham, Barney, Kublin, James, Gilbert, Peter, Corey, Lawrence, Goepfert, Paul, McElrath, M, Johnson, R, Huang, Yunda, and Frahm, Nicole
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AIDS Vaccines ,Adolescent ,Adult ,CD4-Positive T-Lymphocytes ,CD8-Positive T-Lymphocytes ,Double-Blind Method ,Epitopes ,Female ,HIV Antigens ,Humans ,Male ,Middle Aged ,Vaccination ,Young Adult ,env Gene Products ,Human Immunodeficiency Virus ,gag Gene Products ,Human Immunodeficiency Virus - Abstract
T cell responses have been implicated in reduced risk of HIV acquisition in uninfected persons and control of viral replication in HIV-infected individuals. HIV Gag-specific T cells have been predominantly associated with post-infection control, whereas Env antigens are the target for protective antibodies; therefore, inclusion of both antigens is common in HIV vaccine design. However, inclusion of multiple antigens may provoke antigenic competition, reducing the potential effectiveness of the vaccine. HVTN 084 was a randomized, multicenter, double-blind phase 1 trial to investigate whether adding Env to a Gag/Pol vaccine decreases the magnitude or breadth of Gag/Pol-specific T cell responses. Fifty volunteers each received one intramuscular injection of 1 × 1010 particle units (PU) of rAd5 Gag/Pol and EnvA/B/C (3:1:1:1 mixture) or 5 × 109 PU of rAd5 Gag/Pol. CD4+ T cell responses to Gag/Pol measured 4 weeks after vaccination by cytokine expression were significantly higher in the group vaccinated without Env, whereas CD8+ T cell responses did not differ significantly between the two groups. Mapping of individual epitopes revealed greater breadth of the Gag/Pol-specific T cell response in the absence of Env compared to Env coimmunization. Addition of an Env component to a Gag/Pol vaccine led to reduced Gag/Pol CD4+ T cell response rate and magnitude as well as reduced epitope breadth, confirming the presence of antigenic competition. Therefore, T cell-based vaccine strategies should aim at choosing a minimalist set of antigens to reduce interference of individual vaccine components with the induction of the maximally achievable immune response.
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- 2019
4. GeoVax Labs receives notice of allowance for HIV Vaccine patent
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HIV (Viruses) ,Vaccination ,HIV antigens ,AIDS vaccines -- Intellectual property ,Business ,News, opinion and commentary - Abstract
GeoVax Labs announced that the U.S. Patent and Trademark Office has issued a Notice of Allowance for Patent Application No. 17/409,574 titled 'Multivalent HIV Vaccine Boost Compositions and Methods of [...]
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- 2023
5. Suboptimal stimulation by weak agonist epitope variants does not drive dysfunction of HIV-1-specific cytotoxic T lymphocyte clones.
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Grossman, Mark A, Hofmann, Christian, Ng, Hwee L, and Yang, Otto O
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Infectious Diseases ,HIV/AIDS ,Cytokines ,Cytotoxicity Tests ,Immunologic ,Epitopes ,T-Lymphocyte ,HIV Antigens ,HIV-1 ,Humans ,T-Lymphocytes ,Cytotoxic ,anergy ,cytotoxic T lymphocytes ,dysfunction ,exhaustion ,peripheral T-cell tolerance ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Virology ,Biomedical and clinical sciences ,Health sciences - Abstract
ObjectiveTo assess whether weakly recognized epitope variants induce anergy in HIV-1-specific CD8 T lymphocyte (CTL) clones as a mechanism of dysfunction.DesignHIV-1-specific CTL clones were exposed to suboptimally recognized epitope variants, and screened for anergy and other T-cell dysfunction markers, and subsequent capability to kill target cells bearing index epitope.MethodsIn addition to the optimally recognized index epitope, two suboptimally recognized epitope variants were selected based on titration curves for killing of peptide-labeled target cells by three HIV-1-specific CTL clones targeting the epitopes SLYNTVATL (Gag 77-85, A02-restricted), RPAEPVPLQL (Rev 66-75, B07-restricted), and KRWIIMGLNK (Gag 263-272, B27-restricted). Consequences of suboptimal stimulation were assessed by cytokine secretion, gene expression, and capacity to kill index epitope-labeled target cells upon rechallenge.ResultsSuboptimal recognition of epitope variants reduced cytokine production by CTL similarly to reduction in killing of target cells. Gene expression profiles after suboptimal stimulation demonstrated no patterns consistent with T-cell dysfunction due to anergy, exhaustion, or apoptosis. Preexposure of CTL to epitope variants had no discernable impact on their subsequent capacity to kill index epitope-bearing target cells.ConclusionOur data explore the hypothesis that poorly recognized epitope variants not only facilitate HIV-1 evasion of CTL recognition, but also induce CTL dysfunction through suboptimal signaling causing anergy. However, the results do not suggest that suboptimal signaling induces anergy (or exhaustion or apoptosis), indicating that the major role of CTL epitope variation is likely viral escape.
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- 2019
6. Replication-Competent NYVAC-KC Yields Improved Immunogenicity to HIV-1 Antigens in Rhesus Macaques Compared to Nonreplicating NYVAC.
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Kibler, Karen V, Asbach, Benedikt, Perdiguero, Beatriz, García-Arriaza, Juan, Yates, Nicole L, Parks, Robert, Stanfield-Oakley, Sherry, Ferrari, Guido, Montefiori, David C, Tomaras, Georgia D, Roederer, Mario, Foulds, Kathryn E, Forthal, Donald N, Seaman, Michael S, Self, Steve, Gottardo, Raphael, Phogat, Sanjay, Tartaglia, James, Barnett, Susan, Cristillo, Anthony D, Weiss, Deborah, Galmin, Lindsey, Ding, Song, Heeney, Jonathan L, Esteban, Mariano, Wagner, Ralf, Pantaleo, Giuseppe, and Jacobs, Bertram L
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Vaccine Related (AIDS) ,Biotechnology ,Prevention ,Immunization ,HIV/AIDS ,Vaccine Related ,Infectious Diseases ,Prevention of disease and conditions ,and promotion of well-being ,3.4 Vaccines ,Infection ,Good Health and Well Being ,Animals ,Antibodies ,Neutralizing ,CD4-Positive T-Lymphocytes ,HIV Antibodies ,HIV Antigens ,HIV Infections ,HIV-1 ,Humans ,Macaca mulatta ,Male ,Vaccination ,Vaccinia virus ,Viral Vaccines ,Virus Replication ,env Gene Products ,Human Immunodeficiency Virus ,Gag-Pol-Nef ,HIV ,NYVAC ,NYVAC-KC ,T cell response ,antibody responses ,gp140 ,nonhuman primates ,vaccines ,Biological Sciences ,Agricultural and Veterinary Sciences ,Medical and Health Sciences ,Virology ,Agricultural ,veterinary and food sciences ,Biological sciences ,Biomedical and clinical sciences - Abstract
As part of the continuing effort to develop an effective HIV vaccine, we generated a poxviral vaccine vector (previously described) designed to improve on the results of the RV144 phase III clinical trial. The construct, NYVAC-KC, is a replication-competent, attenuated recombinant of the vaccinia virus strain NYVAC. NYVAC is a vector that has been used in many previous clinical studies but is replication deficient. Here, we report a side-by-side comparison of replication-restricted NYVAC and replication-competent NYVAC-KC in a nonhuman primate study, which utilized a prime-boost regimen similar to that of RV144. NYVAC-C and NYVAC-C-KC express the HIV-1 antigens gp140, and Gag/Gag-Pol-Nef-derived virus-like particles (VLPs) from clade C and were used as the prime, with recombinant virus plus envelope protein used as the boost. In nearly every T and B cell immune assay against HIV-1, including neutralization and antibody binding, NYVAC-C-KC induced a greater immune response than NYVAC-C, indicating that replication competence in a poxvirus may improve upon the modestly successful regimen used in the RV144 clinical trial.IMPORTANCE Though the RV144 phase III clinical trial showed promise that an effective vaccine against HIV-1 is possible, a successful vaccine will require improvement over the vaccine candidate (ALVAC) used in the RV144 study. With that goal in mind, we have tested in nonhuman primates an attenuated but replication-competent vector, NYVAC-KC, in direct comparison to its parental vector, NYVAC, which is replication restricted in human cells, similar to the ALVAC vector used in RV144. We have utilized a prime-boost regimen for administration of the vaccine candidate that is similar to the one used in the RV144 study. The results of this study indicate that a replication-competent poxvirus vector may improve upon the effectiveness of the RV144 clinical trial vaccine candidate.
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- 2019
7. Priming with a Potent HIV-1 DNA Vaccine Frames the Quality of Immune Responses prior to a Poxvirus and Protein Boost.
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Asbach, Benedikt, Kibler, Karen V, Köstler, Josef, Perdiguero, Beatriz, Yates, Nicole L, Stanfield-Oakley, Sherry, Tomaras, Georgia D, Kao, Shing-Fen, Foulds, Kathryn E, Roederer, Mario, Seaman, Michael S, Montefiori, David C, Parks, Robert, Ferrari, Guido, Forthal, Donald N, Phogat, Sanjay, Tartaglia, James, Barnett, Susan W, Self, Steven G, Gottardo, Raphael, Cristillo, Anthony D, Weiss, Deborah E, Galmin, Lindsey, Ding, Song, Heeney, Jonathan L, Esteban, Mariano, Jacobs, Bertram L, Pantaleo, Giuseppe, and Wagner, Ralf
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Prevention ,Vaccine Related ,HIV/AIDS ,Biotechnology ,Immunization ,Rare Diseases ,Vaccine Related (AIDS) ,Prevention of disease and conditions ,and promotion of well-being ,3.4 Vaccines ,Infection ,Good Health and Well Being ,Animals ,Antibodies ,Neutralizing ,HIV Antibodies ,HIV Antigens ,HIV Infections ,HIV-1 ,Humans ,Macaca mulatta ,Male ,Poxviridae ,T-Lymphocytes ,Vaccination ,Vaccines ,DNA ,Vaccinia virus ,Viral Vaccines ,Virus Replication ,DNA vaccine ,Gag-Pol-Nef ,NYVAC ,NYVAC-KC ,T cell responses ,antibody responses ,gp140 ,human immunodeficiency virus ,nonhuman primates ,vaccine ,Biological Sciences ,Agricultural and Veterinary Sciences ,Medical and Health Sciences ,Virology ,Agricultural ,veterinary and food sciences ,Biological sciences ,Biomedical and clinical sciences - Abstract
The use of heterologous immunization regimens and improved vector systems has led to increases in immunogenicity of HIV-1 vaccine candidates in nonhuman primates. In order to resolve interrelations between different delivery modalities, three different poxvirus boost regimens were compared. Three groups of rhesus macaques were each primed with the same DNA vaccine encoding Gag, Pol, Nef, and gp140. The groups were then boosted with either the vaccinia virus strain NYVAC or a variant with improved replication competence in human cells, termed NYVAC-KC. The latter was administered either by scarification or intramuscularly. Finally, macaques were boosted with adjuvanted gp120 protein to enhance humoral responses. The regimen elicited very potent CD4+ and CD8+ T cell responses in a well-balanced manner, peaking 2 weeks after the boost. T cells were broadly reactive and polyfunctional. All animals exhibited antigen-specific humoral responses already after the poxvirus boost, which further increased following protein administration. Polyclonal reactivity of IgG antibodies was highest against HIV-1 clade C Env proteins, with considerable cross-reactivity to other clades. Substantial effector functional activities (antibody-dependent cell-mediated cytotoxicity and antibody-dependent cell-mediated virus inhibition) were observed in serum obtained after the last protein boost. Notably, major differences between the groups were absent, indicating that the potent priming induced by the DNA vaccine initially framed the immune responses in such a way that the subsequent boosts with NYVAC and protein led only to an increase in the response magnitudes without skewing the quality. This study highlights the importance of selecting the best combination of vector systems in heterologous prime-boost vaccination regimens.IMPORTANCE The evaluation of HIV vaccine efficacy trials indicates that protection would most likely correlate with a polyfunctional immune response involving several effector functions from all arms of the immune system. Heterologous prime-boost regimens have been shown to elicit vigorous T cell and antibody responses in nonhuman primates that, however, qualitatively and quantitatively differ depending on the respective vector systems used. The present study evaluated a DNA prime and poxvirus and protein boost regimen and compared how two poxvirus vectors with various degrees of replication capacity and two different delivery modalities-conventional intramuscular delivery and percutaneous delivery by scarification-impact several immune effectors. It was found that despite the different poxvirus boosts, the overall immune responses in the three groups were similar, suggesting the potent DNA priming as the major determining factor of immune responses. These findings emphasize the importance of selecting optimal priming agents in heterologous prime-boost vaccination settings.
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- 2019
8. Ancestral sequences from an elite neutralizer proximal to the development of neutralization resistance as a potential source of HIV vaccine immunogens
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Mesa, Kathryn A, Yu, Bin, Wrin, Terri, Petropoulos, Christos J, Pogson, Grant H, Alexander, David L, Perez, Gerardo, O’Rourke, Sara M, Sinangil, Faruk, Robinson, Joseph, Conant, Marcus A, and Berman, Phillip W
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Sexually Transmitted Infections ,Vaccine Related ,Immunization ,Infectious Diseases ,Biotechnology ,Vaccine Related (AIDS) ,HIV/AIDS ,Prevention ,Prevention of disease and conditions ,and promotion of well-being ,3.4 Vaccines ,Infection ,Good Health and Well Being ,AIDS Vaccines ,Broadly Neutralizing Antibodies ,Epitopes ,HIV ,HIV Antibodies ,HIV Antigens ,HIV Infections ,Humans ,Immunogenicity ,Vaccine ,Neutralization Tests ,Phylogeny ,Proviruses ,env Gene Products ,Human Immunodeficiency Virus ,General Science & Technology - Abstract
A major challenge in HIV vaccine development is the identification of immunogens able to elicit broadly neutralizing antibodies (bNAbs). While remarkable progress has been made in the isolation and characterization of bNAbs, the epitopes they recognize appear to be poorly immunogenic. Thus, none of the candidate vaccines developed to date has induced satisfactory levels of neutralizing antibodies to the HIV envelope protein (Env). One approach to the problem of poor immunogenicity is to build vaccines based on envelope (env) genes retrieved from rare individuals termed elite neutralizers (ENs) who at one time possessed specific sequences that stimulated the formation of bNAbs. Env proteins selected from these individuals could possess uncommon, yet to be defined, structural features that enhance the immunogenicity of epitopes recognized by bNAbs. Here we describe the recovery of envs from an EN that developed unusually broad and potent bNAbs. As longitudinal specimens were not available, we combined plasma and provirus sequences acquired from a single time-point to infer a phylogenetic tree. Combining ancestral reconstruction data with virus neutralization data allowed us to sift through the myriad of virus quasi-species that evolved in this individual to identify envelope sequences from the nodes that appeared to define the transition from neutralization sensitive envs to the neutralization resistant envs that occur in EN plasma. Synthetic genes from these nodes were functional in infectivity assays and sensitive to neutralization by bNAbs, and may provide a novel source of immunogens for HIV vaccine development.
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- 2019
9. Performance comparison of the Maxim and Sedia Limiting Antigen Avidity assays for HIV incidence surveillance
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Sempa, Joseph B, Welte, Alex, Busch, Michael P, Hall, Jake, Hampton, Dylan, Facente, Shelley N, Keating, Sheila M, Marson, Kara, Parkin, Neil, Pilcher, Christopher D, Murphy, Gary, Grebe, Eduard, and Assays, on behalf of the Consortium for the Evaluation and Performance of HIV Incidence
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Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Infectious Diseases ,Sexually Transmitted Infections ,HIV/AIDS ,Infection ,Good Health and Well Being ,Algorithms ,Cross-Sectional Studies ,Epidemics ,Female ,HIV Antigens ,HIV Infections ,HIV-1 ,Humans ,Incidence ,Kenya ,Population Surveillance ,Viral Load ,Consortium for the Evaluation and Performance of HIV Incidence Assays ,General Science & Technology - Abstract
BackgroundTwo manufacturers, Maxim Biomedical and Sedia Biosciences Corporation, supply CDC-approved versions of the HIV-1 Limiting Antigen Avidity EIA (LAg) for detecting 'recent' HIV infection in cross-sectional incidence estimation. This study assesses and compares the performance of the two assays for incidence surveillance.MethodsWe ran both assays on a panel of 2,500 well-characterized HIV-1-infected specimens. We analysed concordance of assay results, assessed reproducibility using repeat testing and estimated mean durations of recent infection (MDRIs) and false-recent rates (FRRs) for a range of normalized optical density (ODn) thresholds, alone and in combination with viral load thresholds. We defined three hypothetical surveillance scenarios, similar to the Kenyan and South African epidemics, and a concentrated epidemic. These scenarios allowed us to evaluate the precision of incidence estimates obtained by means of various recent infection testing algorithms (RITAs) based on each of the two assays.ResultsThe Maxim assay produced lower ODn values than the Sedia assay on average, largely as a result of higher calibrator readings (mean OD of 0.749 vs. 0.643), with correlation of normalized readings lower (R2 = 0.908 vs. R2 = 0.938). Reproducibility on blinded control specimens was slightly better for Maxim. The MDRI of a Maxim-based algorithm at the 'standard' threshold (ODn ≤1.5 & VL >1,000) was 201 days (95% CI: 180,223) and for Sedia 171 (152,191). The difference Differences in MDRI were estimated at 32.7 (22.9,42.8) and 30.9 days (21.7,40.7) for the two algorithms, respectively. Commensurately, the Maxim algorithm had a higher FRR in treatment-naive subjects (1.7% vs. 1.1%). The two assays produced similar precision of incidence estimates in the three surveillance scenarios.ConclusionsDifferences between the assays can be primarily attributed to the calibrators supplied by the manufacturers. Performance for surveillance was extremely similar, although different thresholds were optimal (i.e. produced the lowest variance of incidence estimates) and at any given ODn threshold, different estimates of MDRI and FRR were obtained. The two assays cannot be treated as interchangeable: assay and algorithm-specific performance characteristic estimates must be used for survey planning and incidence estimation.
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- 2019
10. Performance of the BioPlex 2200 HIV Ag-Ab assay for identifying acute HIV infection
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Eshleman, Susan H, Piwowar-Manning, Estelle, Sivay, Mariya V, Debevec, Barbara, Veater, Stephanie, McKinstry, Laura, Bekker, Linda-Gail, Mannheimer, Sharon, Grant, Robert M, Chesney, Margaret A, Coates, Thomas J, Koblin, Beryl A, and Fogel, Jessica M
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Sexually Transmitted Infections ,Biotechnology ,HIV/AIDS ,Infectious Diseases ,4.1 Discovery and preclinical testing of markers and technologies ,Infection ,Acute Retroviral Syndrome ,Africa ,Southern ,HIV ,HIV Antibodies ,HIV Antigens ,Humans ,Immunoenzyme Techniques ,Limit of Detection ,RNA ,Viral ,Reagent Kits ,Diagnostic ,Retrospective Studies ,United States ,Viral Load ,Acute ,Ag/Ab assay ,BioPlex ,Microbiology ,Clinical Sciences ,Virology ,Clinical sciences ,Medical microbiology - Abstract
BackgroundAssays that detect HIV antigen (Ag) and antibody (Ab) can be used to screen for HIV infection.ObjectivesTo compare the performance of the BioPlex 2200 HIV Ag-Ab assay and two other Ag/Ab combination assays for detection of acute HIV infection.Study designSamples were obtained from 24 individuals (18 from the US, 6 from South Africa); these individuals were classified as having acute infection based on the following criteria: positive qualitative RNA assay; two negative rapid tests; negative discriminatory test. The samples were tested with the BioPlex assay, the ARCHITECT HIV Ag/Ab Combo test, the Bio-Rad GS HIV Combo Ag-Ab EIA test, and a viral load assay.ResultsTwelve (50.0%) of 24 samples had RNA detected only ( > 40 to 13,476 copies/mL). Ten (43.5%) samples had reactive results with all three Ag/Ab assays, one sample was reactive with the ARCHITECT and Bio-Rad assays, and one sample was reactive with the Bio-Rad and BioPlex assays. The 11 samples that were reactive with the BioPlex assay had viral loads from 83,010 to >750,000 copies/mL; 9/11 samples were classified as Ag positive/Ab negative by the BioPlex assay.ConclusionsDetection of acute HIV infection was similar for the BioPlex assay and two other Ag/Ab assays. All three tests were less sensitive than a qualitative RNA assay and only detected HIV Ag when the viral load was high. The BioPlex assay detected acute infection in about half of the cases, and identified most of those infections as Ag positive/Ab negative.
- Published
- 2018
11. Computational analysis of antibody dynamics identifies recent HIV-1 infection
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Seaton, Kelly E, Vandergrift, Nathan A, Deal, Aaron W, Rountree, Wes, Bainbridge, John, Grebe, Eduard, Anderson, David A, Sawant, Sheetal, Shen, Xiaoying, Yates, Nicole L, Denny, Thomas N, Liao, Hua-Xin, Haynes, Barton F, Robb, Merlin L, Parkin, Neil, Santos, Breno R, Garrett, Nigel, Price, Matthew A, Naniche, Denise, Duerr, Ann C, Keating, Sheila, Hampton, Dylan, Facente, Shelley, Marson, Kara, Welte, Alex, Pilcher, Christopher D, Cohen, Myron S, and Tomaras, Georgia D
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HIV/AIDS ,Vaccine Related (AIDS) ,Prevention ,Infectious Diseases ,Pediatric AIDS ,Vaccine Related ,Pediatric ,Immunization ,Infection ,Good Health and Well Being ,Antibody Affinity ,Antigen-Antibody Reactions ,Biomarkers ,Computational Biology ,HIV Antibodies ,HIV Antigens ,HIV Infections ,HIV-1 ,Humans ,Immunoglobulin G ,Incidence ,Retrospective Studies ,Time Factors ,CEPHIA group ,AIDS/HIV ,Antigen ,Immunoglobulins ,Immunology - Abstract
Accurate HIV-1 incidence estimation is critical to the success of HIV-1 prevention strategies. Current assays are limited by high false recent rates (FRRs) in certain populations and a short mean duration of recent infection (MDRI). Dynamic early HIV-1 antibody response kinetics were harnessed to identify biomarkers for improved incidence assays. We conducted retrospective analyses on circulating antibodies from known recent and longstanding infections and evaluated binding and avidity measurements of Env and non-Env antigens and multiple antibody forms (i.e., IgG, IgA, IgG3, IgG4, dIgA, and IgM) in a diverse panel of 164 HIV-1-infected participants (clades A, B, C). Discriminant function analysis identified an optimal set of measurements that were subsequently evaluated in a 324-specimen blinded biomarker validation panel. These biomarkers included clade C gp140 IgG3, transmitted/founder clade C gp140 IgG4 avidity, clade B gp140 IgG4 avidity, and gp41 immunodominant region IgG avidity. MDRI was estimated at 215 day or alternatively, 267 days. FRRs in untreated and treated subjects were 5.0% and 3.6%, respectively. Thus, computational analysis of dynamic HIV-1 antibody isotype and antigen interactions during infection enabled design of a promising HIV-1 recency assay for improved cross-sectional incidence estimation.
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- 2017
12. Infection Staging and Incidence Surveillance Applications of High Dynamic Range Diagnostic Immuno-Assay Platforms
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Grebe, Eduard, Welte, Alex, Hall, Jake, Keating, Sheila M, Facente, Shelley N, Marson, Kara, Martin, Jeffrey N, Little, Susan J, Price, Matthew A, Kallas, Esper G, Busch, Michael P, Pilcher, Christopher D, and Murphy, Gary
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Medical Microbiology ,Biomedical and Clinical Sciences ,Infectious Diseases ,Sexually Transmitted Infections ,HIV/AIDS ,Infection ,Diagnostic Tests ,Routine ,HIV Antibodies ,HIV Antigens ,HIV Infections ,HIV-1 ,Humans ,Immunoassay ,Incidence ,Population Surveillance ,Sensitivity and Specificity ,Time Factors ,Clinical Sciences ,Public Health and Health Services ,Virology ,Clinical sciences ,Epidemiology ,Public health - Abstract
BackgroundCustom HIV staging assays, including the Sedia HIV-1 Limiting Antigen (LAg) Avidity EIA and avidity modifications of the Ortho VITROS anti-HIV-1+2 and Abbott ARCHITECT HIV Ag/Ab Combo assays, are used to identify "recent" infections in clinical settings and for cross-sectional HIV incidence estimation. However, the high dynamic range of chemiluminescent platforms allows differentiating recent and long-standing infection on signal intensity, and this raises the prospect of using unmodified diagnostic assays for infection timing and surveillance applications.MethodsWe tested a panel of 2500 well-characterized specimens with estimable duration of HIV infection with the 3 assays and the unmodified ARCHITECT. Regression models were used to estimate mean durations of recent infection (MDRIs), context-specific false-recent rates (FRRs) and correlation between diagnostic signal intensity and LAg measurements. Hypothetical epidemiological scenarios were constructed to evaluate utility in surveillance applications.ResultsOver a range of MDRIs (reflecting recency discrimination thresholds), a diluted ARCHITECT-based RITA produced lower FRRs than the VITROS platform (FRR ≈ 0.5% and 1.5%, respectively at MDRI ≈ 200 days), and the unmodified diagnostic ARCHITECT produces incidence estimates with comparable precision to LAg (relative SE ≈ 17.5% and 15%, respectively at MDRI ≈ 200 days). ARCHITECT S/CO measurements were highly correlated with LAg optical density measurements (r = 0.80), and values below 200 are strongly predictive of LAg recency and duration of infection less than 1 year.ConclusionsLow quantitative measurements from the unmodified ARCHITECT obviate the need for additional recency testing, and its use is feasible in clinical staging and incidence surveillance applications.
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- 2017
13. BCG immunization-induced KLRG1+ NK cells show memory-like responses to mycobacterial and HIV antigens
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HIV (Viruses) ,Vaccination ,BCG vaccines ,HIV antigens ,BCG ,Tuberculosis vaccines ,Tuberculosis ,Killer cells ,Viral proteins ,Pharmaceuticals and cosmetics industries ,Health ,Science and technology - Abstract
2024 MAY 27 (NewsRx) -- By a News Reporter-Staff News Editor at AIDS Vaccine Week -- According to news reporting based on a preprint abstract, our journalists obtained the following [...]
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- 2024
14. Evaluating New Approaches to Developing AIDS Vaccines by Creating Virus-like Particles that Display HIV Antigens or by Using Live, Attenuated (Weakened), non-HIV Viruses to Express HIV Proteins
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HIV (Viruses) ,HIV antigens ,AIDS (Disease) ,AIDS vaccines ,Viral proteins ,Pharmaceuticals and cosmetics industries ,Health ,Science and technology - Abstract
2024 MAY 20 (NewsRx) -- By a News Reporter-Staff News Editor at AIDS Vaccine Week -- Principal Investigator: Ira Berkower, MD, PhD Office / Division / Lab: OVRR / DVP [...]
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- 2024
15. Researchers from University of North Carolina Chapel Hill Report Findings in HIV/AIDS (Nanoparticle Delivery of Tat Synergizes With Classical Latency Reversal Agents To Express Hiv Antigen Targets).
- Abstract
Researchers from the University of North Carolina Chapel Hill have conducted a study on HIV/AIDS, specifically focusing on the limited cellular levels of the HIV transcriptional activator Tat as a contributor to proviral latency. The researchers found that lipid nanoparticles containing HIV tat mRNA can induce HIV expression in primary CD4 T cells. They also discovered that combining small molecule inhibitors with Tat delivered to CD4 T cells is a promising approach to effectively target the HIV reservoir. This research has been peer-reviewed and published in Antimicrobial Agents and Chemotherapy. [Extracted from the article]
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- 2024
16. HIV Antibody Level as a Marker of HIV Persistence and Low-Level Viral Replication
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Keating, Sheila M, Pilcher, Christopher D, Jain, Vivek, Lebedeva, Mila, Hampton, Dylan, Abdel-Mohsen, Mohamed, Deng, Xutao, Murphy, Gary, Welte, Alex, Facente, Shelley N, Hecht, Frederick, Deeks, Steven G, Pillai, Satish K, and Busch, Michael P
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Infectious Diseases ,Sexually Transmitted Infections ,HIV/AIDS ,Biotechnology ,Infection ,Antiretroviral Therapy ,Highly Active ,Biomarkers ,Gene Expression Profiling ,HIV Antibodies ,HIV Antigens ,HIV Infections ,HIV-1 ,Humans ,Longitudinal Studies ,RNA ,Viral ,Specimen Handling ,Viral Load ,Virus Replication ,Antibodies ,HIV persistence ,latent reservoir ,incidence assay ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundHuman immunodeficiency virus (HIV) antibodies are generated and maintained by ongoing systemic expression of HIV antigen. We investigated whether HIV antibody responses as measured by high-throughput quantitative and qualitative assays could be used to indirectly measure persistent HIV replication in individuals receiving antiretroviral therapy (ART).MethodsHIV antibody responses were measured over time in the presence or absence of suppressive ART and were compared to the HIV reservoir size and expression of antiviral restriction factors.ResultsAmong untreated individuals, including both elite controllers (ie, persons with a viral load of ≤40 copies/mL) and noncontrollers, antibody parameters were stable over time and correlated with the individual viral load. Viral suppression with ART led to a progressive decline in antibody responses after treatment induction that persisted for 5-7 years. Higher levels of HIV antibodies during suppressive therapy were associated with later initiation of ART after infection, with higher DNA and cell-associated RNA levels, and with lower expression of multiple anti-HIV host restriction factors.DiscussionThese findings suggest that declining antibody levels during ART reflect lower levels of antigen production and/or viral replication in the persistent HIV reservoir. Results of relatively inexpensive and quantitative HIV antibody assays may be useful indirect markers that enable efficient monitoring of the viral reservoir and suppression during functional-cure interventions.
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- 2017
17. Real-world performance of the new US HIV testing algorithm in medical settings
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Marson, Kara G, Marlin, Robert, Pham, Phong, Cohen, Stephanie E, Jones, Diane, Roemer, Marguerite, Peters, Philip J, Haller, Barbara, and Pilcher, Christopher D
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Biomedical and Clinical Sciences ,Clinical Sciences ,HIV/AIDS ,Clinical Research ,Health Services ,Prevention ,Mental Health ,Infectious Diseases ,Detection ,screening and diagnosis ,4.2 Evaluation of markers and technologies ,Infection ,Good Health and Well Being ,AIDS Serodiagnosis ,Algorithms ,Clinical Laboratory Techniques ,Female ,HIV Antibodies ,HIV Antigens ,HIV Infections ,Humans ,Immunoassay ,Male ,Mass Screening ,Nucleic Acid Amplification Techniques ,Sensitivity and Specificity ,Viral Load ,HIV ,Diagnostics ,Assay evaluation ,4th-generation ,ARCHITECT ,Microbiology ,Medical Microbiology ,Virology ,Clinical sciences ,Medical microbiology - Abstract
BackgroundOur medical center laboratory recently adapted its 24/7, two-hourly testing program to use an ARCHITECT-Multispot-viral load (AR-MS-VL) algorithm in place of a previous rapid test-immunofluorescence (RT-IF) algorithm.ObjectivesWe evaluated screening test performance, acute case detection, turnaround time and ability to resolve HIV status under the new algorithm.Study designWe considered consecutive HIV tests from January to November 2015. AR-MS-VL results at Zuckerberg San Francisco General Hospital and Trauma Center (ZSFG) were compared with RT-IF results at ZSFG and also with AR-MS-VL results in the recently completed CDC Screening Targeted Populations to Interrupt On-going Chains of HIV Transmission with Enhanced Partner Notification (STOP) Study for targeted testing of MSM at publicly funded testing sites in San Francisco.ResultsAmong 21,985 HIV tests performed at ZSFG, 16,467 were tested by RT-IF and 5518 by AR-MS-VL. There were 321 HIV infections detected, of which 274 (84%) were known HIV+ cases, and 47 were newly identified HIV infections. Considering only patients of HIV-negative or -unknown status, prevalence was 0.22%. Under the AR-MS-VL algorithm, turnaround times for screening results and full algorithm results were 3 and 21h; status-unresolved cases were reduced (from 47% to 22%) compared with the RT-IF algorithm. The positive predictive value (PPV) of a new-positive AR screening test was low (0.44) at ZSFG, where no acute infections were detected. At STOP Study sites where HIV prevalence was higher and acute infection was more common, the AR PPV was higher (0.93). All 24 false-positive AR screening tests at ZSFG had a signal/cutoff (S/CO) ratio of 15. Of 62 acute infections in the STOP Study, 23 (37%) had an S/CO
- Published
- 2017
18. Structural basis for germline antibody recognition of HIV-1 immunogens.
- Author
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Scharf, Louise, West, Anthony P, Sievers, Stuart A, Chen, Courtney, Jiang, Siduo, Gao, Han, Gray, Matthew D, McGuire, Andrew T, Scheid, Johannes F, Nussenzweig, Michel C, Stamatatos, Leonidas, and Bjorkman, Pamela J
- Subjects
Humans ,HIV-1 ,HIV Envelope Protein gp120 ,HIV Antibodies ,HIV Antigens ,Crystallography ,X-Ray ,Protein Conformation ,Protein Binding ,Models ,Molecular ,Antibodies ,Neutralizing ,HIV ,biophysics ,broadly neutralizing antibodies ,crystallography ,human ,immunology ,structural biology ,virus ,Crystallography ,X-Ray ,Models ,Molecular ,Antibodies ,Neutralizing ,HIV/AIDS ,Prevention ,Vaccine related ,Vaccine Related ,Immunization ,Biochemistry and Cell Biology - Abstract
Efforts to elicit broadly neutralizing antibodies (bNAbs) against HIV-1 require understanding germline bNAb recognition of HIV-1 envelope glycoprotein (Env). The VRC01-class bNAb family derived from the VH1-2*02 germline allele arose in multiple HIV-1-infected donors, yet targets the CD4-binding site on Env with common interactions. Modified forms of the 426c Env that activate germline-reverted B cell receptors are candidate immunogens for eliciting VRC01-class bNAbs. We present structures of germline-reverted VRC01-class bNAbs alone and complexed with 426c-based gp120 immunogens. Germline bNAb-426c gp120 complexes showed preservation of VRC01-class signature residues and gp120 contacts, but detectably different binding modes compared to mature bNAb-gp120 complexes. Unlike typical antibody-antigen interactions, VRC01-class germline antibodies exhibited preformed antigen-binding conformations for recognizing immunogens. Affinity maturation introduced substitutions increasing induced-fit recognition and electropositivity, potentially to accommodate negatively-charged complex-type N-glycans on gp120. These results provide general principles relevant to the unusual evolution of VRC01-class bNAbs and guidelines for structure-based immunogen design.
- Published
- 2016
19. Patent Issued for HIV vaccination compositions comprising vaccinia VLPS and plant-produced VLPS presenting HIV antigens (USPTO 11918642)
- Subjects
HIV (Viruses) ,Vaccination ,HIV antigens ,Viral proteins ,Health - Abstract
2024 MAR 25 (NewsRx) -- By a News Reporter-Staff News Editor at AIDS Weekly -- A patent by the inventors Jacobs, Bertram (Tempe, AZ, US), Kibler, Karen (Scottsdale, AZ, US), [...]
- Published
- 2024
20. Evaluating New Approaches to Developing AIDS Vaccines by Creating Virus-like Particles that Display HIV Antigens or by Using Live, Attenuated (Weakened), non-HIV Viruses to Express HIV Proteins
- Subjects
HIV (Viruses) ,HIV antigens ,AIDS (Disease) ,AIDS vaccines ,Viral proteins ,Pharmaceuticals and cosmetics industries ,Health ,Science and technology - Abstract
2024 MAR 18 (NewsRx) -- By a News Reporter-Staff News Editor at AIDS Vaccine Week -- Principal Investigator: Ira Berkower, MD, PhD Office / Division / Lab: OVRR / DVP [...]
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- 2024
21. GeoVax Receives Notice of Allowance for the HIV Vaccine Patent
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HIV (Viruses) ,Biological products industry -- Intellectual property ,Vaccination ,HIV antigens ,Cancer vaccines -- Intellectual property ,AIDS vaccines -- Intellectual property ,General interest ,News, opinion and commentary - Abstract
ATLANTA: GeoVax Labs, Inc. (Nasdaq: GOVX), a biotechnology company developing immunotherapies and vaccines against cancers and infectious diseases, today announced that the U.S. Patent and Trademark Office has issued a [...]
- Published
- 2023
22. Methamphetamine Use in HIV-infected Individuals Affects T-cell Function and Viral Outcome during Suppressive Antiretroviral Therapy.
- Author
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Massanella, Marta, Gianella, Sara, Schrier, Rachel, Dan, Jennifer M, Pérez-Santiago, Josué, Oliveira, Michelli F, Richman, Douglas D, Little, Susan J, Benson, Constance A, Daar, Eric S, Dube, Michael P, Haubrich, Richard H, Smith, Davey M, and Morris, Sheldon R
- Subjects
T-Lymphocytes ,Monocytes ,Humans ,HIV Infections ,Methamphetamine ,Receptors ,CCR5 ,DNA ,Viral ,HIV Antigens ,Treatment Outcome ,Antiretroviral Therapy ,Highly Active ,Case-Control Studies ,Cell Proliferation ,Adult ,Middle Aged ,Drug Abuse (NIDA Only) ,Prevention ,HIV/AIDS ,Substance Abuse ,Clinical Research ,Infectious Diseases ,2.1 Biological and endogenous factors ,Infection ,Adult *Antiretroviral Therapy ,Highly Active Case-Control Studies Cell Proliferation DNA ,Viral/analysis HIV Antigens/immunology HIV Infections/*drug therapy/*immunology/virology Humans Methamphetamine/*therapeutic use Middle Aged Monocytes/immunology Receptors ,CCR5/metabolism T-Lymphocytes/*immunology Treatment Outcome - Abstract
We investigated the associations between methamphetamine (meth) use, immune function, and the dynamics of HIV and cytomegalovirus [CMV] in the blood and genital tract of HIV-infected ART-suppressed subjects. Self-reported meth use was associated with increased CD4(+) and CD8(+) T-cell proliferation (Ki67(+), p
- Published
- 2015
23. Determination of HIV Status in African Adults With Discordant HIV Rapid Tests
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Fogel, Jessica M, Piwowar-Manning, Estelle, Donohue, Kelsey, Cummings, Vanessa, Marzinke, Mark A, Clarke, William, Breaud, Autumn, Fiamma, Agnès, Donnell, Deborah, Kulich, Michal, Mbwambo, Jessie KK, Richter, Linda, Gray, Glenda, Sweat, Michael, Coates, Thomas J, and Eshleman, Susan H
- Subjects
Infectious Diseases ,HIV/AIDS ,Clinical Research ,Pediatric ,Pediatric AIDS ,Detection ,screening and diagnosis ,4.2 Evaluation of markers and technologies ,Infection ,Adult ,HIV Antibodies ,HIV Antigens ,HIV Infections ,Humans ,Immunoassay ,Sensitivity and Specificity ,South Africa ,Tanzania ,Time Factors ,HIV ,rapid test ,discordant ,Africa ,Clinical Sciences ,Public Health and Health Services ,Virology - Abstract
BackgroundIn resource-limited settings, HIV infection is often diagnosed using 2 rapid tests. If the results are discordant, a third tie-breaker test is often used to determine HIV status. This study characterized samples with discordant rapid tests and compared different testing strategies for determining HIV status in these cases.MethodsSamples were previously collected from 173 African adults in a population-based survey who had discordant rapid test results. Samples were classified as HIV positive or HIV negative using a rigorous testing algorithm that included two fourth-generation tests, a discriminatory test, and 2 HIV RNA tests. Tie-breaker tests were evaluated, including rapid tests (1 performed in-country), a third-generation enzyme immunoassay, and two fourth-generation tests. Selected samples were further characterized using additional assays.ResultsTwenty-nine samples (16.8%) were classified as HIV positive and 24 of those samples (82.8%) had undetectable HIV RNA. Antiretroviral drugs were detected in 1 sample. Sensitivity was 8.3%-43% for the rapid tests; 24.1% for the third-generation enzyme immunoassay; 95.8% and 96.6% for the fourth-generation tests. Specificity was lower for the fourth-generation tests than the other tests. Accuracy ranged from 79.5% to 91.3%.ConclusionsIn this population-based survey, most HIV-infected adults with discordant rapid tests were virally suppressed without antiretroviral drugs. Use of individual assays as tie-breaker tests was not a reliable method for determining HIV status in these individuals. More extensive testing algorithms that use a fourth-generation screening test with a discriminatory test and HIV RNA test are preferable for determining HIV status in these cases.
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- 2015
24. Performance of the fourth-generation Bio-Rad GS HIV Combo Ag/Ab enzyme immunoassay for diagnosis of HIV infection in Southern Africa
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Piwowar-Manning, Estelle, Fogel, Jessica M, Richardson, Paul, Wolf, Shauna, Clarke, William, Marzinke, Mark A, Fiamma, Agnès, Donnell, Deborah, Kulich, Michal, Mbwambo, Jessie KK, Richter, Linda, Gray, Glenda, Sweat, Michael, Coates, Thomas J, and Eshleman, Susan H
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Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Immunology ,Infectious Diseases ,Clinical Research ,Prevention ,HIV/AIDS ,Infection ,Africa ,Southern ,HIV ,HIV Antibodies ,HIV Antigens ,HIV Core Protein p24 ,HIV Infections ,HIV-1 ,HIV-2 ,Humans ,Immunoenzyme Techniques ,Reagent Kits ,Diagnostic ,Reproducibility of Results ,Sensitivity and Specificity ,Fourth-generation ,Diagnosis ,Africa ,Enzyme immunoassay ,Microbiology ,Virology ,Clinical sciences ,Medical microbiology - Abstract
BackgroundFourth-generation HIV assays detect both antigen and antibody, facilitating detection of acute/early HIV infection. The Bio-Rad GS HIV Combo Ag/Ab assay (Bio-Rad Combo) is an enzyme immunoassay that simultaneously detects HIV p24 antigen and antibodies to HIV-1 and HIV-2 in serum or plasma.ObjectiveTo evaluate the performance of the Bio-Rad Combo assay for detection of HIV infection in adults from Southern Africa.Study designSamples were obtained from adults in Soweto and Vulindlela, South Africa and Dar es Salaam, Tanzania (300 HIV-positive samples; 300 HIV-negative samples; 12 samples from individuals previously classified as having acute/early HIV infection). The samples were tested with the Bio-Rad Combo assay. Additional testing was performed to characterize the 12 acute/early samples.ResultsAll 300 HIV-positive samples were reactive using the Bio-Rad Combo assay; false positive test results were obtained for 10 (3.3%) of the HIV-negative samples (sensitivity: 100%, 95% confidence interval [CI]: 98.8-100%); specificity: 96.7%, 95% CI: 94.0-98.4%). The assay detected 10 of the 12 infections classified as acute/early. The two infections that were not detected had viral loads
- Published
- 2015
25. A High Throughput Protein Microarray Approach to Classify HIV Monoclonal Antibodies and Variant Antigens.
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Dotsey, Emmanuel Y, Gorlani, Andrea, Ingale, Sampat, Achenbach, Chad J, Forthal, Donald N, Felgner, Philip L, and Gach, Johannes S
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Humans ,HIV-1 ,HIV Infections ,Polysaccharides ,Peptides ,Antibodies ,Monoclonal ,HIV Antibodies ,HIV Antigens ,Enzyme-Linked Immunosorbent Assay ,Protein Array Analysis ,Cluster Analysis ,Sequence Alignment ,Antibody Specificity ,Amino Acid Sequence ,Kinetics ,Molecular Sequence Data ,High-Throughput Screening Assays ,Antibodies ,Monoclonal ,General Science & Technology - Abstract
In recent years, high throughput discovery of human recombinant monoclonal antibodies (mAbs) has been applied to greatly advance our understanding of the specificity, and functional activity of antibodies against HIV. Thousands of antibodies have been generated and screened in functional neutralization assays, and antibodies associated with cross-strain neutralization and passive protection in primates, have been identified. To facilitate this type of discovery, a high throughput-screening tool is needed to accurately classify mAbs, and their antigen targets. In this study, we analyzed and evaluated a prototype microarray chip comprised of the HIV-1 recombinant proteins gp140, gp120, gp41, and several membrane proximal external region peptides. The protein microarray analysis of 11 HIV-1 envelope-specific mAbs revealed diverse binding affinities and specificities across clades. Half maximal effective concentrations, generated by our chip analysis, correlated significantly (P
- Published
- 2015
26. Researchers Submit Patent Application, "Sialydase Linked Hiv Antibodies And Methods Of Use", for Approval (USPTO 20240181051).
- Abstract
A patent application has been submitted for a composition that aims to enhance the ability of natural killer (NK) cells to target HIV-infected cells. The composition includes a targeting domain specific for binding to an HIV antigen and a domain for desialylation of HIV-infected cells. The desialylation domain contains a neuraminidase enzyme, such as NEU1, NEU2, NEU3, NEU4, or a bacterial or viral neuraminidase. This composition could potentially be used to prevent or treat HIV or associated diseases. [Extracted from the article]
- Published
- 2024
27. BCG immunization-induced KLRG1+ NK cells show memory-like responses to mycobacterial and HIV antigens.
- Abstract
A recent study investigated the effect of the BCG vaccine on Natural Killer (NK) cells, a subset of the innate immune system, and their ability to develop memory-like responses to HIV antigens. The study found that BCG vaccine-induced KLRG1+ NK cells showed memory-like responses to both Mycobacterium tuberculosis (MTB) and HIV antigens, as evidenced by their increased production of IFNγ when exposed to these antigens. This finding is significant because co-infection with HIV and TB is prevalent in Asia and Africa, where BCG is administered. Understanding these responses is crucial for the development of more effective vaccines and therapeutics for both TB and HIV. [Extracted from the article]
- Published
- 2024
28. Evaluating New Approaches to Developing AIDS Vaccines by Creating Virus-like Particles that Display HIV Antigens or by Using Live, Attenuated (Weakened), non-HIV Viruses to Express HIV Proteins.
- Abstract
This article discusses the challenges faced by scientists in developing a safe and effective vaccine against HIV, the virus that causes AIDS. One challenge is to stimulate the immune system to produce durable and broadly neutralizing antibodies that can protect against the diverse strains of HIV. Another challenge is to elicit strong T cell immunity to HIV proteins. The article describes two strategies being used to increase vaccine potency: incorporating HIV antigens into virus-like particles (VLPs) and using a live attenuated rubella virus as a vector to carry HIV genes. These approaches have shown promising results in animal studies and provide new insights for developing HIV/AIDS vaccines. [Extracted from the article]
- Published
- 2024
29. A VRC13-like bNAb response is associated with complex escape pathways in HIV-1 envelope.
- Author
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Joshi VR, Claiborne DT, Pack ML, Power KA, Newman RM, Batorsky R, Bean DJ, Goroff MS, Lingwood D, Seaman MS, Rosenberg E, and Allen TM
- Subjects
- Humans, Amino Acids, CD4 Antigens genetics, env Gene Products, Human Immunodeficiency Virus genetics, Epitopes, HIV Antibodies, HIV Antigens, HIV Envelope Protein gp120 genetics, HIV Seropositivity, HIV-1 genetics, AIDS Vaccines immunology, Broadly Neutralizing Antibodies immunology, HIV Infections
- Abstract
The rational design of HIV-1 immunogens to trigger the development of broadly neutralizing antibodies (bNAbs) requires understanding the viral evolutionary pathways influencing this process. An acute HIV-1-infected individual exhibiting >50% plasma neutralization breadth developed neutralizing antibody specificities against the CD4-binding site (CD4bs) and V1V2 regions of Env gp120. Comparison of pseudoviruses derived from early and late autologous env sequences demonstrated the development of >2 log resistance to VRC13 but not to other CD4bs-specific bNAbs. Mapping studies indicated that the V3 and CD4-binding loops of Env gp120 contributed significantly to developing resistance to the autologous neutralizing response and that the CD4-binding loop (CD4BL) specifically was responsible for the developing resistance to VRC13. Tracking viral evolution during the development of this cross-neutralizing CD4bs response identified amino acid substitutions arising at only 4 of 11 known VRC13 contact sites (K282, T283, K421, and V471). However, each of these mutations was external to the V3 and CD4BL regions conferring resistance to VRC13 and was transient in nature. Rather, complete resistance to VRC13 was achieved through the cooperative expression of a cluster of single amino acid changes within and immediately adjacent to the CD4BL, including a T359I substitution, exchange of a potential N -linked glycosylation (PNLG) site to residue S362 from N363, and a P369L substitution. Collectively, our data characterize complex HIV-1 env evolution in an individual developing resistance to a VRC13-like neutralizing antibody response and identify novel VRC13-associated escape mutations that may be important to inducing VRC13-like bNAbs for lineage-based immunogens.IMPORTANCEThe pursuit of eliciting broadly neutralizing antibodies (bNAbs) through vaccination and their use as therapeutics remains a significant focus in the effort to eradicate HIV-1. Key to our understanding of this approach is a more extensive understanding of bNAb contact sites and susceptible escape mutations in HIV-1 envelope ( env ). We identified a broad neutralizer exhibiting VRC13-like responses, a non-germline restricted class of CD4-binding site antibody distinct from the well-studied VRC01-class. Through longitudinal envelope sequencing and Env-pseudotyped neutralization assays, we characterized a complex escape pathway requiring the cooperative evolution of four amino acid changes to confer complete resistance to VRC13. This suggests that VRC13-class bNAbs may be refractory to rapid escape and attractive for therapeutic applications. Furthermore, the identification of longitudinal viral changes concomitant with the development of neutralization breadth may help identify the viral intermediates needed for the maturation of VRC13-like responses and the design of lineage-based immunogens., Competing Interests: The authors declare no conflict of interest.
- Published
- 2024
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- View/download PDF
30. Laboratory-based evaluation of the 4th-generation AlereTM HIV Combo rapid point-of-care test.
- Author
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Manjate A, Nilsson C, Axelsson M, Lindroth S, Sirbu D, Sacarlal J, Andersson S, and Unemo M
- Subjects
- Female, Humans, HIV Antibodies, HIV Core Protein p24, Point-of-Care Testing, HIV Antigens, Sensitivity and Specificity, RNA, HIV-2, HIV Infections diagnosis, HIV Infections epidemiology, HIV Seropositivity, HIV-1 genetics
- Abstract
Background: Mozambique is a high-prevalence country for HIV and early detection of new HIV infections is crucial for control of the epidemic. We aimed to evaluate the accuracy of the 4th-generation rapid diagnostic test (RDT) AlereTM HIV Combo in detecting acute and seroconverted HIV-infection, among sexually-active women attending three clinical health centers in Maputo, Mozambique., Methods: Women aged 14-55 years (n = 920) seeking care at the Mavalane Health Area, Maputo (February 2018-January 2019) were included, and blood specimens sampled. Sociodemographic and sexual behavior data were collected. Point-of-care HIV testing was performed using Alere DetermineTM HIV-1/2 and Uni-GoldTM HIV-1/2. All samples were also tested using Enzygnost® HIV Integral 4 and Innotest® HIV Antigen mAb in laboratory. The 4th-generation RDT AlereTM HIV Combo was evaluated on serum samples in the laboratory. Finally, Innotest® HIV Antigen mAb, Enzygnost® HIV Integral 4 (Ag/Ab), and HIV RNA quantification acted as gold standard assays in the evaluation of AlereTM HIV Combo test for HIV antigen detection (in clinical samples and in three HIV-1 seroconversion panels)., Results: The antibody component of the 4th generation AlereTM HIV Combo RDT demonstrated a sensitivity and specificity of 100% examining clinical samples. However, the test did not detect HIV p24 antigen in any clinical samples, while Innotest® HIV Antigen mAb, verified by Enzygnost® HIV Integral 4 (Ag/Ab) and/or HIV RNA quantification, detected HIV antigen in six clinical samples. Furthermore, the AlereTM HIV Combo RDT had a low sensitivity in the detection of HIV p24 antigen in seroconversion panels. The HIV prevalence among the examined women was 17.8%., Conclusions: The 4th-generation RDT AlereTM HIV Combo showed similar sensitivity to the 3rd-generation RDTs to detect seroconverted HIV-infections. However, the sensitivity for detection of HIV p24 antigen and diagnosing acute HIV infections, before seroconversion, was low. There is an urgent need to develop and evaluate simple and affordable POC tests with high sensitivity and specificity for diagnosing individuals with acute HIV infection in resource-limited settings with high HIV prevalence., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Manjate et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2024
- Full Text
- View/download PDF
31. Evaluating New Approaches to Developing AIDS Vaccines by Creating Virus-like Particles that Display HIV Antigens or by Using Live, Attenuated (Weakened), non-HIV Viruses to Express HIV Proteins.
- Published
- 2024
32. Reflexiones humanísticas en un servicio de atención especializado en VIH.
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Barros Branco, Bianca, Chagas Barreto, Amanda, de Azevedo Silva, Rafael, Fecury Tavares, Lorena, and Paulino Cordeiro, Herbert
- Subjects
MEDICAL personnel ,MEDICAL students ,HIV ,OUTPATIENT medical care ,COMMUNICABLE diseases - Abstract
Copyright of Revista Bioetica is the property of Conselho Federal de Medicina and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2020
- Full Text
- View/download PDF
33. Sequential broadening of CTL responses in early HIV-1 infection is associated with viral escape.
- Author
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Karlsson, Annika C, Iversen, Astrid KN, Chapman, Joan M, de Oliviera, Tulio, Spotts, Gerald, McMichael, Andrew J, Davenport, Miles P, Hecht, Frederick M, and Nixon, Douglas F
- Subjects
T-Lymphocytes ,Cytotoxic ,Humans ,HIV-1 ,HIV Infections ,Disease Progression ,Tumor Necrosis Factor-alpha ,HLA-A2 Antigen ,HIV Antigens ,Epitopes ,Amino Acid Substitution ,Sequence Alignment ,Evolution ,Molecular ,Phylogeny ,Base Sequence ,Consensus Sequence ,Sequence Homology ,Nucleic Acid ,Molecular Sequence Data ,Female ,Male ,gag Gene Products ,Human Immunodeficiency Virus ,pol Gene Products ,Human Immunodeficiency Virus ,nef Gene Products ,Human Immunodeficiency Virus ,Interferon-gamma ,Immune Evasion ,T-Lymphocytes ,Cytotoxic ,Evolution ,Molecular ,Sequence Homology ,Nucleic Acid ,gag Gene Products ,Human Immunodeficiency Virus ,pol Gene Products ,nef Gene Products ,General Science & Technology - Abstract
BackgroundAntigen-specific CTL responses are thought to play a central role in containment of HIV-1 infection, but no consistent correlation has been found between the magnitude and/or breadth of response and viral load changes during disease progression.Methods and findingsWe undertook a detailed investigation of longitudinal CTL responses and HIV-1 evolution beginning with primary infection in 11 untreated HLA-A2 positive individuals. A subset of patients developed broad responses, which selected for consensus B epitope variants in Gag, Pol, and Nef, suggesting CTL-induced adaptation of HIV-1 at the population level. The patients who developed viral escape mutations and broad autologous CTL responses over time had a significantly higher increase in viral load during the first year of infection compared to those who did not develop viral escape mutations.ConclusionsA continuous dynamic development of CTL responses was associated with viral escape from temporarily effective immune responses. Our results suggest that broad CTL responses often represent footprints left by viral CTL escape rather than effective immune control, and help explain earlier findings that fail to show an association between breadth of CTL responses and viral load. Our results also demonstrate that CTL pressures help to maintain certain elements of consensus viral sequence, which likely represent viral escape from common HLA-restricted CTL responses. The ability of HIV to evolve to escape CTL responses restricted by a common HLA type highlights the challenges posed to development of an effective CTL-based vaccine.
- Published
- 2007
34. Immune Selection for Altered Antigen Processing Leads to Cytotoxic T Lymphocyte Escape in Chronic HIV-1 Infection
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Draenert, Rika, Le Gall, Sylvie, Pfafferott, Katja J, Leslie, Alasdair J, Chetty, Polan, Brander, Christian, Holmes, Edward C, Chang, Shih-Chung, Feeney, Margaret E, Addo, Marylyn M, Ruiz, Lidia, Ramduth, Danni, Jeena, Prakash, Altfeld, Marcus, Thomas, Stephanie, Tang, Yanhua, Verrill, Cori L, Dixon, Catherine, Prado, Julia G, Kiepiela, Photini, Martinez-Picado, Javier, Walker, Bruce D, and Goulder, Philip JR
- Subjects
Prevention ,Genetics ,Infectious Diseases ,HIV/AIDS ,Vaccine Related ,Immunization ,Vaccine Related (AIDS) ,Aetiology ,2.1 Biological and endogenous factors ,Inflammatory and immune system ,Infection ,Alleles ,Amino Acid Sequence ,Antigen Presentation ,Base Sequence ,Clone Cells ,DNA ,Viral ,Epitopes ,Gene Products ,gag ,Genetic Variation ,HIV Antigens ,HIV Infections ,HIV-1 ,HLA-B Antigens ,Humans ,Molecular Sequence Data ,Mutation ,Sequence Homology ,Amino Acid ,T-Lymphocytes ,Cytotoxic ,Medical and Health Sciences ,Immunology - Abstract
Mutations within cytotoxic T lymphocyte (CTL) epitopes impair T cell recognition, but escape mutations arising in flanking regions that alter antigen processing have not been defined in natural human infections. In human histocompatibility leukocyte antigen (HLA)-B57+ HIV-infected persons, immune selection pressure leads to a mutation from alanine to proline at Gag residue 146 immediately preceding the NH2 terminus of a dominant HLA-B57-restricted epitope, ISPRTLNAW. Although N-extended wild-type or mutant peptides remained well-recognized, mutant virus-infected CD4 T cells failed to be recognized by the same CTL clones. The A146P mutation prevented NH2-terminal trimming of the optimal epitope by the endoplasmic reticulum aminopeptidase I. These results demonstrate that allele-associated sequence variation within the flanking region of CTL epitopes can alter antigen processing. Identifying such mutations is of major relevance in the construction of vaccine sequences.
- Published
- 2004
35. ANALYSIS OF SERODIFFERENT PARTNERS IN THE HIV REFERENCE SERVICE.
- Author
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Barbosa Felix, Jefferson Felipe, Vieira, Marina, Xavier de Matos, Geilton, Silva Araújo, Luana Matos, Pinto de Moura, Josely, and Dully Andrade, Raquel
- Abstract
Copyright of Journal of Nursing UFPE / Revista de Enfermagem UFPE is the property of Revista de Enfermagem UFPE and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2019
- Full Text
- View/download PDF
36. "Ww-Domain-Activated Extracellular Vesicles Targeting Hiv" in Patent Application Approval Process (USPTO 20230390382).
- Abstract
A patent application by inventors from Harvard College has been made available online for a new method of developing an effective HIV vaccine. The application describes the use of novel extracellular vesicles (EVs) containing WW-domain containing proteins to target HIV antigens, specifically the membrane proximal external region (MPER) peptide. The MPER peptide is a relatively invariant region of the HIV envelope protein and is a potential target for vaccine development. The fusion proteins described in the application consist of a WW-containing domain, a transmembrane domain, and an extracellular domain that is an HIV antigen domain. These fusion proteins can be displayed on the surface of EVs to elicit the production of neutralizing antibodies against HIV. The patent application also includes claims for isolated nucleic acids encoding the fusion proteins, as well as methods of delivering the EVs to a subject. [Extracted from the article]
- Published
- 2023
37. Utility of the Signal-to-Cutoff Ratio and Antigen Index from Fourth- and Fifth-Generation HIV-1/HIV-2 Antigen/Antibody Assays for the Diagnosis of Acute HIV Infection: Applicability for Real-Time Use for Immediate Initiation of Antiretroviral Therapy
- Author
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Elena Whitney, David Pitrak, Kathleen G. Beavis, Nicholas M. Moore, Shivanjali Shankaran, Ana Precy Abeleda, Jessica Schmitt, and Beverly E. Sha
- Subjects
Immunoassay ,Microbiology (medical) ,HIV Antigens ,Virology ,HIV-2 ,HIV-1 ,Humans ,HIV Infections ,HIV Antibodies ,Sensitivity and Specificity - Abstract
Identification of individuals with acute HIV infection (AHI) and rapid initiation of antiretroviral therapy (ART) are priorities for HIV elimination efforts. Fourth- and fifth-generation HIV-1/HIV-2 antigen (Ag)/antibody (Ab) combination assays can quickly identify patients with AHI, but false-positive results can occur. Confirmatory nucleic acid amplification testing (NAAT) may not be rapidly available. We reviewed the data for 127 patients with positive fourth-generation ARCHITECT and fifth-generation Bio-Plex immunoassay results who had negative or indeterminate confirmatory Ab testing results, which yielded 38 patients with confirmed AHI and 89 patients with false-positive results. The receiver operating characteristic (ROC) curves showed excellent discriminatory power, with an area under the curve (AUC) for the signal-to-cutoff (S/CO) ratio of 0.970 (95% confidence interval [CI], 0.935 to 1.00) and an AUC for the Ag index (AI) of 0.968 (95% CI, 0.904 to 1.00). A threshold of 3.78 for the S/CO ratio would maximize the sensitivity (96.3%) and specificity (93.4%). The threshold for AI was 2.83 (sensitivity of 100% and specificity of 96.4%). The S/CO ratio was significantly correlated with the viral load (Spearman correlation coefficient, 0.486 [P = 0.014]), but the AI was not. The viral loads were all high, with a median of >2.8 million copies/mL. Two false-positive results with AI and S/CO ratio values markedly higher than the medians were observed, indicating that biological false-positive results can occur. Review of the S/CO ratio or AI may be used to improve the accuracy of AHI diagnosis prior to confirmatory NAAT results being available.
- Published
- 2022
38. Antigenic molecular mimicry in viral-mediated protection from cancer: the HIV case
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Carmen Manolio, Concetta Ragone, Beatrice Cavalluzzo, Angela Mauriello, Maria Lina Tornesello, Franco M. Buonaguro, Angelo Salomone Megna, Giovanna D’Alessio, Roberta Penta, Maria Tagliamonte, and Luigi Buonaguro
- Subjects
Male ,HIV Antigens ,Colonic Neoplasms ,Molecular Mimicry ,Receptors, Antigen, T-Cell ,Epitopes, T-Lymphocyte ,Humans ,HIV Infections ,General Medicine ,CD8-Positive T-Lymphocytes ,General Biochemistry, Genetics and Molecular Biology - Abstract
Background People living with HIV/AIDS (PLWHA) show a reduced incidence for three cancer types, namely breast, prostate and colon cancers. In the present study, we assessed whether a molecular mimicry between HIV epitopes and tumor associated antigens and, consequently, a T cell cross-reactivity could provide an explanation for such an epidemiological evidence. Methods Homology between published TAAs and non-self HIV-derived epitopes have been assessed by BLAST homology. Structural analyses have been performed by bioinformatics tools. Immunological validation of CD8+ T cell cross-reactivity has been evaluated ex vivo by tetramer staining. Findings Sequence homologies between multiple TAAs and HIV epitopes have been found. High structural similarities between the paired TAAs and HIV epitopes as well as comparable patterns of contact with HLA and TCR α and β chains have been observed. Furthermore, cross-reacting CD8+ T cells have been identified. Interpretation This is the first study showing a molecular mimicry between HIV antigens an TAAs identified in breast, prostate and colon cancers. Therefore, it is highly reasonable that memory CD8+ T cells elicited during the HIV infection may play a key role in controlling development and progression of such cancers in the PLWHA lifetime. This represents the first demonstration ever that a viral infection may induce a natural “preventive” anti-cancer memory T cells, with highly relevant implications beyond the HIV infection.
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- 2022
39. Antibody and cellular responses to HIV vaccine regimens with DNA plasmid as compared with ALVAC priming: An analysis of two randomized controlled trials
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Moodie, Zoe, Walsh, Stephen R., Laher, Fatima, Maganga, Lucas, Herce, Michael E., Naidoo, Sarita, Hosseinipour, Mina C., Innes, Craig, Bekker, Linda-Gail, Grunenberg, Nicole, Mann, Philipp, Yu, Chenchen, deCamp, Allan C., Miner, Maurine D., Yates, Nicole L., Heptinstall, Jack, Mkhize, Nonhlanhla N., Dintwe, One, Frahm, Nicole, Cohen, Kristen W., Allen, Mary, Hutter, Julia, Wagner, Ralf, Pantaleo, Giuseppe, McElrath, M. Juliana, Tomaras, Georgia D., Morris, Lynn, Montefiori, David C., Andersen-Nissen, Erica, Gray, Glenda E., Gilbert, Peter B., and Kublin, James G.
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Clinical trials ,AIDS vaccines ,Genetic research ,HIV antigens ,HIV -- Drug therapy ,DNA ,Vaccination ,T cells ,Biological sciences - Abstract
Background DNA plasmids promise a pragmatic alternative to viral vectors for prime-boost HIV-1 vaccines. We evaluated DNA plasmid versus canarypox virus (ALVAC) primes in 2 randomized, double-blind, placebo-controlled trials in southern Africa with harmonized trial designs. HIV Vaccine Trials Network (HVTN) 111 tested DNA plasmid prime by needle or needleless injection device (Biojector) and DNA plasmid plus gp120 protein plus MF59 adjuvant boost. HVTN 100 tested ALVAC prime and ALVAC plus gp120 protein plus MF59 adjuvant boost (same protein/adjuvant as HVTN 111) by needle. Methods and findings The primary endpoints for this analysis were binding antibody (bAb) responses to HIV antigens (gp120 from strains ZM96, 1086, and TV1; variable 1 and 2 [V1V2] regions of gp120 from strains TV1, 1086, and B.CaseA, as 1086 V1V2 and B.CaseA were correlates of risk in the RV144 efficacy trial), neutralizing antibody (nAb) responses to pseudoviruses TV1c8.2 and MW925.26, and cellular responses to vaccine-matched antigens (envelope [Env] from strains ZM96, 1086, and TV1; and Gag from strains LAI and ZM96) at month 6.5, two weeks after the fourth vaccination. Per-protocol cohorts included vaccine recipients from HVTN 100 (n = 186, 60% male, median age 23 years) enrolled between February 9, 2015, and May 26, 2015 and from HVTN 111 (n = 56, 48% male, median age 24 years) enrolled between June 21, 2016, and July 13, 2017. IgG bAb response rates were 100% to 3 Env gp120 antigens in both trials. Response rates to V1V2 were lower and similar in both trials except to vaccine-matched 1086 V1V2, with rates significantly higher for the DNA-primed regimen than the ALVAC-primed regimen: 96.6% versus 72.7% (difference = 23.9%, 95% CI 15.6%-32.2%, p < 0.001). Among positive responders, bAb net mean fluorescence intensity (MFI) was significantly higher with the DNA-primed regimen than ALVAC-primed for 1086 V1V2 (geometric mean [GM] 2,833.3 versus 1,200.9; ratio = 2.36, 95% CI 1.42-3.92, p 98% in both trials, with significantly higher 50% inhibitory dilution (ID.sub.50) among DNA-primed positive responders (n = 53) versus ALVAC-primed (n = 182) to tier 1A MW965.26 (GM 577.7 versus 265.7, ratio = 2.17, 95% CI 1.67-2.83, p < 0.001) and to TV1c8.2 (GM 187.3 versus 100.4, ratio = 1.87, 95% CI 1.48-2.35, p < 0.001). CD4+ T-cell response rates were significantly higher with DNA plasmid prime via Biojector than ALVAC prime (91.4% versus 52.8%, difference = 38.6%, 95% CI 20.5%-56.6%, p < 0.001 for ZM96.C; 88.0% versus 43.1%, difference = 44.9%, 95% CI 26.7%-63.1%, p < 0.001 for 1086.C; 55.5% versus 2.2%, difference = 53.3%, 95% CI 23.9%-82.7%, p < 0.001 for Gag LAI/ZM96). The study's main limitations include the nonrandomized comparison of vaccines from 2 different trials, the lack of data on immune responses to other non-vaccine-matched antigens, and the uncertain clinical significance of the observed immunological effects. Conclusions In this study, we found that further investigation of DNA/protein regimens is warranted given enhanced immunogenicity to the V1V2 correlates of decreased HIV-1 acquisition risk identified in RV144, the only HIV vaccine trial to date to show any efficacy., Author(s): Zoe Moodie 1,*, Stephen R. Walsh 2,3,4, Fatima Laher 5, Lucas Maganga 6, Michael E. Herce 7, Sarita Naidoo 8, Mina C. Hosseinipour 9, Craig Innes 10, Linda-Gail Bekker [...]
- Published
- 2020
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40. Cuidado enfermero en paciente portador de VIH con bronconeumonía
- Abstract
Objective: To analyze nursing care in HIV patients with a diagnosis of Bronchopneumonia. Methods: A literature review of scientific papers based on nursing care in HIV patients with a diagnosis of Bronchopneumonia was carried out. Results: 15 scientific articles with relevant contributions were selected within the publication range of 2020 - 2021. Conclusion: The role of the nursing professional is to care for both the healthy and sick person, in all types of activities that contribute to their health or to recover it, it is estimated that 5 to 20% are affected, in this way it is the most frequent etiology in the population infected by the Human Immunodeficiency Virus with higher incidence in the young male population., Objetivo: Analizar los cuidados de enfermería en pacientes portadores de VIH con diagnóstico de Bronco Neumonía. Método: Se realizó una revisión bibliográfica de documentos científicos basados en los cuidados de enfermería en pacientes portadores de VIH con diagnóstico de Bronco Neumonía. Resultados: Se seleccionaron 15 artículos científicos que van en el rango de publicación del 2020 - 2021 con aportaciones relevantes. Conclusión: La función del profesional de enfermería es atender tanto a la persona sana como enferma, en todo tipo de actividades que contribuyen a su salud o a recuperarla, se estima que del 5 al 20% son afectados, de esta manera es la etiología más frecuente en la población infectada por el Virus de Inmunodeficiencia Humana con mayor incidencia en la población masculina joven.
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- 2022
41. Prevalencia de las manifestaciones orales en pacientes con VIH/SIDA
- Abstract
Objective: To know the prevalence of oral manifestations in patients with HIV/AIDS in a national and international context, since this pathology presents a constant growth, in spite of prevention and promotion through the years by different world organizations. Method: bibliographic review. Results: 15 articles have been included, which are congruent with the objective set. Conclusion: Knowledge of the clinical picture of patients with HIV/AIDS and the behavior of the different lesions that may occur, especially oral manifestations, and the treatment plan, should be fundamental for a health professional and even more so for a dentist, since it is in the oral cavity where pathognomonic signs of this epidemic appear., Objetivo: Conocer la prevalencia de las manifestaciones orales en pacientes con VIH/SIDA en un contexto nacional e internacional ya que dicha patología presenta un constante crecimiento, pese a la prevención y promoción a través de los años por parte de diferentes organizaciones mundiales. Método: revisión bibliográfica. Resultados: Se han incluido 15 artículos, de los cuales son congruentes con el objetivo planteado. Conclusión: El conocimiento del cuadro clínico de pacientes que padecen VIH/SIDA y el comportamiento de las diferentes lesiones que puedan presentarse, en especial manifestaciones orales, y plan de tratamiento; debe ser fundamental para un profesional de la salud y más para un Odontólogo, ya que en cavidad oral es en donde surgen signos patognomónicos de esta epidemia.
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- 2022
42. Engaging an HIV vaccine target through the acquisition of low B cell affinity.
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Ronsard L, Yousif AS, Nait Mohamed FA, Feldman J, Okonkwo V, McCarthy C, Schnabel J, Caradonna T, Barnes RM, Rohrer D, Lonberg N, Schmidt A, and Lingwood D
- Subjects
- Humans, Animals, Mice, B-Lymphocytes, Memory B Cells, Receptors, Antigen, B-Cell genetics, Broadly Neutralizing Antibodies, HIV Antigens, Mice, Transgenic, AIDS Vaccines, HIV Infections prevention & control
- Abstract
Low affinity is common for germline B cell receptors (BCR) seeding development of broadly neutralizing antibodies (bnAbs) that engage hypervariable viruses, including HIV. Antibody affinity selection is also non-homogenizing, insuring the survival of low affinity B cell clones. To explore whether this provides a natural window for expanding human B cell lineages against conserved vaccine targets, we deploy transgenic mice mimicking human antibody diversity and somatic hypermutation (SHM) and immunize with simple monomeric HIV glycoprotein envelope immunogens. We report an immunization regimen that focuses B cell memory upon the conserved CD4 binding site (CD4bs) through both conventional affinity maturation and reproducible expansion of low affinity BCR clones with public patterns in SHM. In the latter instance, SHM facilitates target acquisition by decreasing binding strength. This suggests that permissive B cell selection enables the discovery of antibody epitopes, in this case an HIV bnAb site., (© 2023. Springer Nature Limited.)
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- 2023
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43. A novel built-in adjuvant metallothionein-3 aids protein antigens to induce rapid, robust, and durable immune responses
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Ying Yin, Yanfei Gu, Xiaodong Zai, Ruihua Li, Xinjie Zhu, Rui Yu, Jun Zhang, Shuyi Wang, Yue Zhang, Jian Lin, Junjie Xu, and Wei Chen
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Mammals ,Mice ,Adjuvants, Immunologic ,HIV Antigens ,Immunology ,Immunology and Allergy ,Animals ,Humans ,Brucella abortus ,Adaptive Immunity ,Metallothionein 3 ,Adjuvants, Pharmaceutic - Abstract
Adjuvants are crucial components of vaccines that can enhance and modulate antigen-specific immune responses. Herein, we reported for the first time that human metallothionein-3 (MT3), a low molecular weight cysteine-rich metal-binding protein, was a novel promising adjuvant candidate that could help protein antigens to induce rapid, effective, and durable antigen-specific immune responses. In the present study, MT3 was fused to outer membrane protein 19 (Omp19) of Brucella abortus (MT3-Omp19, MO) and C fragment heavy chain (Hc) of tetanus neurotoxin (MT3-Hc, MH), respectively. The results showed that MT3 as a built-in adjuvant increased the Omp19- or Hc-specific antibody responses by 100-1000 folds in seven days after primary immunization. Compared to other commercially available adjuvants, MT3 could stimulate earlier (4 days after primary injection) and stronger (10-100 folds) antibody response with lower antigen dose, and its adjuvanticity relied on fusion to antigen. Although the mechanism was not clear yet, the fusion protein MO was observed to directly activate DCs, promote germinal center formation and improve the speed of Ig class switching. Interestingly, our subsequent study found that other members of the mammalian MT family (human MT1 or murine MT3 for examples) also had potential adjuvant effects, but their effects were lower than human MT3. Overall, this study explored a new function of human MT3 as a novel built-in adjuvant, which may have important clinical application potential in vaccine development against global pandemics.
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- 2022
44. Coordenação motora de crianças e adolescentes portadores do vírus da imunodeficiência humana.
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Marques, Karina Carvalho, de Brito Barbosa Abdon, Chrisna Mayra, Santa Maria, Liliane Bitencourt, Carneiro, Saul Rassy, dos Santos, Márcio Clementino, Ferreira Normando, Valéria Marques, da Silva Dias, George Alberto, Carneiro Nunes, Erica Feio, and da Silva Pontes, Lucieny
- Abstract
Introduction: The Human Immunodeficiency Virus (HIV) is a lentivirus that depresses the immune system, favoring the triggering of deficits, including the motor system. These deficits can be generated through the adverse effects of antiretroviral therapy. Objectives: To describe the motor coordination profile of children and adolescents infected by the HIV and exposed to the use of antiretroviral therapies. Materials and Methods: A cross-sectional, observational study was carried out, in which 34 children and adolescents enrolled in the Maternal and Child Referral Unit of Pará were divided into two groups: 1) Control Group: n=13, with negative HIV serology, but exposed to pre, peri or postnatal medication; and 2) Experimental group: n=21, children seropositive for HIV and prolonged exposure to antiretroviral therapies for more than 1 year. The Korperkoordination test fur Kinder test battery was used for motor performance analysis. Statistical analysis was performed using Bioestat® 5.0 software, considering a significance level of 5%. Results: We identified motor coordination deficit for tasks of balance (p=0.003) and lateralization (p=0.007) compromising the body awareness in the experimental group. The analysis of the global motor quotient and of this with chronological age were also significant, respectively p=0.027 e p=0.003. Conclusion: Children and adolescents infected vertically with the HIV and exposed to antiretroviral therapy had motor performance impairment for the tasks of balance and laterality. [ABSTRACT FROM AUTHOR]
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- 2018
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45. HIV-1 Accessory Proteins: Which one is Potentially Effective in Diagnosis and Vaccine Development?
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Elnaz Agi, Alireza Milani, Azam Bolhassani, Ghazal Marouf, Maryam Ahmadi, and Kazem Baesi
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0301 basic medicine ,HIV Antigens ,viruses ,Human Immunodeficiency Virus Proteins ,030106 microbiology ,Heterologous ,HIV Infections ,HIV Antibodies ,Biochemistry ,Virus ,Serology ,Mice ,03 medical and health sciences ,Immune system ,Antigen ,Structural Biology ,Animals ,Humans ,AIDS Vaccines ,biology ,virus diseases ,General Medicine ,biochemical phenomena, metabolism, and nutrition ,Virology ,Granzyme B ,CTL ,030104 developmental biology ,HIV-1 ,biology.protein ,Antibody ,Biomarkers - Abstract
Background: The combination antiretroviral therapy (cART) could increase the number of circulating naive CD4 T lymphocytes, but was not able to eradicate human immunodeficiency virus-1 (HIV-1) infection. Objective: Thus, induction of strong immune responses is important for control of HIV-1 infection. Furthermore, a simple and perfect serological method is required to detect virus in untreated-, treated- and drug resistant- HIV-1 infected individuals. Methods: This study was conducted to assess and compare immunogenic properties of Nef, Vif, Vpr and Vpu accessory proteins as an antigen candidate in mice and their diagnostic importance in human as a biomarker. Results: Our data showed that in mice, all heterologous prime/ boost regimens were more potent than homologous prime/ boost regimens in eliciting Th1 response and Granzyme B secretion as CTL activity. Moreover, the Nef, Vpu and Vif proteins could significantly increase Th1 immune response. In contrast, the Vpr protein could considerably induce Th2 immune response. On the other hand, among four accessory proteins, HIV-1 Vpu could significantly detect treated group from untreated group as a possible biomarker in human. Conclusion: Generally, among accessory proteins, Nef, Vpu and Vif antigens were potentially more suitable vaccine antigen candidates than Vpr antigen. Human antibodies against all these proteins were higher in HIV-1 different groups than healthy group. Among them, Vpu was known as a potent antigen in diagnosis of treated from untreated individuals. The potency of accessory proteins as an antigen candidate in an animal model and a human cohort study are underway.
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- 2021
46. Patent Issued for Poxvirus vectors encoding HIV antigens, and methods of use thereof (USPTO 11723970).
- Abstract
HIV-1 is the most common and pathogenic strain of the virus, with more than 90% of HIV/AIDS cases deriving from infection with HIV-1 group M. The M group is subdivided further into clades or subtypes. The invention also relates to compositions and methods of using such novel poxvirus vectors comprising nucleic acid sequence encoding the synthetic HIV envelope proteins to induce increased immune responses against HIV-1, particularly HIV-1 clade C and B, preferably when used in combination with other HIV antigens. [Extracted from the article]
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- 2023
47. High expression of HIV-1 matrix protein p17 in both lymphoma and lymph node tissues of AIDS patients
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Yanling Feng, Zhenyan Wang, Dong Zeng, Shu Song, Yuexiang Yang, Ao Wang, Jingjing Xu, Wenjuan Guo, Minmin Wu, Yuhan Shi, Ye Zheng, Duoduo Li, Renfang Zhang, and Hongzhou Lu
- Subjects
Acquired Immunodeficiency Syndrome ,HIV Antigens ,Lymphoma, Non-Hodgkin ,HIV-1 ,Humans ,HIV Infections ,Cell Biology ,Lymph Nodes ,gag Gene Products, Human Immunodeficiency Virus ,Pathology and Forensic Medicine ,Retrospective Studies - Abstract
HIV-1 matrix protein p17 was found to be associated with lymphoma development in vitro. This study aimed to elucidate the pathogenetic roles of HIV-1 p17 in AIDS-related lymphoma.Expression of HIV-1 proteins p17, p24, nef and tat were evaluated in tumor tissue samples from 60 lymphoma patients and lymph node samples from 23 non-lymphoma patients with HIV-1 infection by immunohistochemistry. Microvascular density (MVD) determined by CD34 were also assessed in tumor tissues. Clinicopathological data of AIDS patients with lymphoma were collected retrospectively.The subtypes of lymphoma among sixty AIDS patients were diffuse large B-cell lymphoma (32 cases), Burkitt lymphoma (23 cases), Hodgkin's lymphoma (4 cases), and plasmablastic lymphoma (1 case). The expression rate of HIV-1 p17 in lymphoma and non-lymphoma group was 63 % (38/60) and 61 % (14/29) respectively, with no significant difference (p = 0.835). The positive expression rate of p17 in both groups was significantly higher than that of p24, nef and tat (p 0.05). The expression of p17 was associated with a higher MVD in the lymphoma group (p 0.05). There were no significant differences in the 2-years overall survival between p17 positive and negative group (61 % vs. 50 %, p = 0.525).The common expression of HIV-1 matrix protein p17 in both lymphoma and lymph node tissues of AIDS patients and the association between p17 expression and the higher MVD suggest that the accumulation and persistence of p17 in tissues may play a role in lymphoma development.
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- 2022
48. Feeding Eggs from Hens Immunized with Specific KLH-Conjugated HIV Peptide Candidate Vaccines to Chicks Induces Specific Anti-HIV gp120 and gp41 Antibodies that Neutralize the Original HIV Antigens
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Oliver Pérez, Fisher Smikle, Ferrer Cosme, and Justiz Vaillant
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chemistry.chemical_classification ,Anti hiv ,Reverse vaccinology ,Human immunodeficiency virus (HIV) ,Peptide ,Biology ,Conjugated system ,Gp41 ,medicine.disease_cause ,Virology ,HIV Antigens ,chemistry ,biology.protein ,medicine ,Antibody - Published
- 2020
49. B-cell clonogenic activity of HIV-1 p17 variants is driven by PAR1-mediated EGF transactivation
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Riccardo Dolcetti, Cinzia Giagulli, Francesca Caccuri, Alberto Zani, Pasqualina D'Ursi, Ekta Manocha, Arnaldo Caruso, Alessandro Orro, Simone Zorzan, Antonella Bugatti, and Federica Filippini
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Cancer microenvironment ,Transcriptional Activation ,EXPRESSION ,0301 basic medicine ,Cell biology ,Cancer Research ,Lymphoma ,Carcinogenesis ,HIV Antigens ,PHASE ,TRASTUZUMAB ,Drug development ,HIV Infections ,RAC1 ,Biology ,Lymphocyte Activation ,gag Gene Products, Human Immunodeficiency Virus ,Article ,ANGIOGENESIS ,Phosphatidylinositol 3-Kinases ,03 medical and health sciences ,Transactivation ,PROTEIN-COUPLED RECEPTORS ,0302 clinical medicine ,Growth factor receptor ,medicine ,Humans ,Receptor, PAR-1 ,TRANSCRIPTION ,ACTIVATED RECEPTORS ,Clonogenic assay ,Molecular Biology ,PI3K/AKT/mTOR pathway ,B cell ,Cyclin-dependent kinase 1 ,ABL ,Epidermal Growth Factor ,CANCER ,Oncogene Protein v-akt ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,HIV-1 ,GROWTH-FACTOR RECEPTOR ,LYMPHANGIOGENESIS ,Cancer research ,Molecular Medicine ,Signal Transduction - Abstract
Combined antiretroviral therapy (cART) for HIV-1 dramatically slows disease progression among HIV+individuals. Currently, lymphoma represents the main cause of death among HIV-1-infected patients. Detection of p17 variants (vp17s) endowed with B-cell clonogenic activity in HIV-1-seropositive patients with lymphoma suggests their possible role in lymphomagenesis. Here, we demonstrate that the clonogenic activity of vp17s is mediated by their binding to PAR1 and to PAR1-mediated EGFR transactivation through Gq protein. The entire vp17s-triggered clonogenic process is MMPs dependent. Moreover, phosphoproteomic and bioinformatic analysis highlighted the crucial role of EGFR/PI3K/Akt pathway in modulating several molecules promoting cancer progression, including RAC1, ABL1, p53, CDK1, NPM, Rb, PTP-1B, and STAT1. Finally, we show that a peptide (F1) corresponding to the vp17s functional epitope is sufficient to trigger the PAR1/EGFR/PI3K/Akt pathway and bind PAR1. Our findings suggest novel potential therapeutic targets to counteract vp17-driven lymphomagenesis in HIV+patients.
- Published
- 2020
50. The HIV-1 Matrix Protein p17 Does Cross the Blood-Brain Barrier
- Author
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Lurdes Gano, Miguel A. R. B. Castanho, Vera Neves, Maria Cristina Oliveira, João D. G. Correia, Arnaldo Caruso, Pietro Mazzuca, Francesca Caccuri, and Repositório da Universidade de Lisboa
- Subjects
Chemokine ,HIV Antigens ,Immunology ,Central nervous system ,HIV Infections ,Endosomes ,Pharmacology ,Blood–brain barrier ,gag Gene Products, Human Immunodeficiency Virus ,Microbiology ,Receptors, Interleukin-8B ,Cell Line ,Proinflammatory cytokine ,Mice ,Chemokine receptor ,Virology ,Autophagy ,medicine ,Animals ,Humans ,CXC chemokine receptors ,Cells, Cultured ,Viral matrix protein ,HIV-associated neurocognitive disorder ,In vivo biodistribution ,biology ,Endothelial Cells ,virus diseases ,Bloodbrain barrier ,HIV-1 matrix protein p17 ,Transcytosis ,Virus-Cell Interactions ,Protein Transport ,medicine.anatomical_structure ,Blood-Brain Barrier ,Insect Science ,Host-Pathogen Interactions ,HIV-1 ,biology.protein ,Disease Susceptibility ,Protein Binding - Abstract
© 2022 American Society for Microbiology. All Rights Reserved., Human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorder (HAND) remains an important neurological manifestation in HIV-1-infected (HIV) patients. Furthermore, detection of the HIV-1 matrix protein p17 (p17) in the central nervous system (CNS) and its ability to form toxic assemblies in the brain have been recently confirmed. Here, we show for the first time, using both an in vitro blood-brain barrier (BBB) model and in vivo biodistribution studies in healthy mice, that p17 can cross the BBB. There is rapid brain uptake with 0.35% 0.19% of injected activity per gram of tissue (IA/g) 2 min after administration, followed by brain accumulation with 0.28% 0.09% IA/g after 1 h. The interaction of p17 with chemokine receptor 2 (CXCR2) at the surface of brain endothelial cells triggers transcytosis. The present study supports the hypothesis of a direct role of free p17 in neuronal dysfunction in HAND by demonstrating its intrinsic ability to reach the CNS., This study was supported in part by Associazione Italiana per la Ricerca sul Cancro (AIRC) grant 20108 (to A.C.) and by the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement 828774 (to M.C.)
- Published
- 2022
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