17 results on '"Pitisuttihum P"'
Search Results
2. RV144 HIV-1 vaccination impacts post-infection antibody responses.
- Author
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Thembi Mdluli, Ningbo Jian, Bonnie Slike, Dominic Paquin-Proulx, Gina Donofrio, Aljawharah Alrubayyi, Syna Gift, Rebecca Grande, Mary Bryson, Anna Lee, Vincent Dussupt, Letzibeth Mendez-Riveria, Eric Sanders-Buell, Agnès-Laurence Chenine, Ursula Tran, Yifan Li, Eric Brown, Paul T Edlefsen, Robert O'Connell, Peter Gilbert, Sorachai Nitayaphan, Punnee Pitisuttihum, Supachai Rerks-Ngarm, Merlin L Robb, Robert Gramzinski, Galit Alter, Sodsai Tovanabutra, Ivelin S Georgiev, Margaret E Ackerman, Victoria R Polonis, Sandhya Vasan, Nelson L Michael, Jerome H Kim, Michael A Eller, Shelly J Krebs, and Morgane Rolland
- Subjects
Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
The RV144 vaccine efficacy clinical trial showed a reduction in HIV-1 infections by 31%. Vaccine efficacy was associated with stronger binding antibody responses to the HIV Envelope (Env) V1V2 region, with decreased efficacy as responses wane. High levels of Ab-dependent cellular cytotoxicity (ADCC) together with low plasma levels of Env-specific IgA also correlated with decreased infection risk. We investigated whether B cell priming from RV144 vaccination impacted functional antibody responses to HIV-1 following infection. Antibody responses were assessed in 37 vaccine and 63 placebo recipients at 6, 12, and 36 months following HIV diagnosis. The magnitude, specificity, dynamics, subclass recognition and distribution of the binding antibody response following infection were different in RV144 vaccine recipients compared to placebo recipients. Vaccine recipients demonstrated increased IgG1 binding specifically to V1V2, as well as increased IgG2 and IgG4 but decreased IgG3 to HIV-1 Env. No difference in IgA binding to HIV-1 Env was detected between the vaccine and placebo recipients following infection. RV144 vaccination limited the development of broadly neutralizing antibodies post-infection, but enhanced Fc-mediated effector functions indicating B cell priming by RV144 vaccination impacted downstream antibody function. However, these functional responses were not associated with clinical markers of disease progression. These data reveal that RV144 vaccination primed B cells towards specific binding and functional antibody responses following HIV-1 infection.
- Published
- 2020
- Full Text
- View/download PDF
3. Human papillomavirus detection in cervical neoplasia attributed to 12 high-risk human papillomavirus genotypes by region
- Author
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Xavier Castellsagué, Kevin A. Ault, F. Xavier Bosch, Darron Brown, Jack Cuzick, Daron G. Ferris, Elmar A. Joura, Suzanne M. Garland, Anna R Giuliano, Mauricio Hernandez-Avila, Warner Huh, Ole-Erik Iversen, Susanne K. Kjaer, Joaquin Luna, Joseph Monsonego, Nubia Muñoz, Evan Myers, Jorma Paavonen, Punnee Pitisuttihum, Marc Steben, Cosette M. Wheeler, Gonzalo Perez, Alfred Saah, Alain Luxembourg, Heather L Sings, and Christine Velicer
- Subjects
Infectious and parasitic diseases ,RC109-216 - Abstract
Background: We estimated the proportion of cervical intraepithelial neoplasia (CIN) cases attributed to 14 HPV types, including quadrivalent (qHPV) (6/11/16/18) and 9-valent (9vHPV) (6/11/16/18/31/33/45/52/58) vaccine types, by region Methods: Women ages 15–26 and 24–45 years from 5 regions were enrolled in qHPV vaccine clinical trials. Among 10,706 women (placebo arms), 1539 CIN1, 945 CIN2/3, and 24 adenocarcinoma in situ (AIS) cases were diagnosed by pathology panel consensus. Results: Predominant HPV types were 16/51/52/56 (anogenital infection), 16/39/51/52/56 (CIN1), and 16/31/52/58 (CIN2/3). In regions with largest sample sizes, minimal regional variation was observed in 9vHPV type prevalence in CIN1 (~50%) and CIN2/3 (81–85%). Types 31/33/45/52/58 accounted for 25–30% of CIN1 in Latin America and Europe, but 14–18% in North America and Asia. Types 31/33/45/52/58 accounted for 33–38% of CIN2/3 in Latin America (younger women), Europe, and Asia, but 17–18% of CIN2/3 in Latin America (older women) and North America. Non-vaccine HPV types 35/39/51/56/59 had similar or higher prevalence than qHPV types in CIN1 and were attributed to 2–11% of CIN2/3. Conclusions: The 9vHPV vaccine could potentially prevent the majority of CIN1-3, irrespective of geographic region. Notwithstanding, non-vaccine types 35/39/51/56/59 may still be responsible for some CIN1, and to a lesser extent CIN2/3. Keywords: Human papillomavirus, Cervical cancer, Cervical intraepithelial neoplasia, Adenocarcinoma in situ
- Published
- 2016
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4. Vaccine-induced Human Antibodies Specific for the Third Variable Region of HIV-1 gp120 Impose Immune Pressure on Infecting Viruses
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Susan Zolla-Pazner, Paul T. Edlefsen, Morgane Rolland, Xiang-Peng Kong, Allan deCamp, Raphael Gottardo, Constance Williams, Sodsai Tovanabutra, Sandra Sharpe-Cohen, James I. Mullins, Mark S. deSouza, Nicos Karasavvas, Sorachai Nitayaphan, Supachai Rerks-Ngarm, Punnee Pitisuttihum, Jaranit Kaewkungwal, Robert J. O'Connell, Merlin L. Robb, Nelson L. Michael, Jerome H. Kim, and Peter Gilbert
- Subjects
HIV ,Antibody ,Vaccine ,Clinical trial ,Medicine ,Medicine (General) ,R5-920 - Abstract
To evaluate the role of V3-specific IgG antibodies (Abs) in the RV144 clinical HIV vaccine trial, which reduced HIV-1 infection by 31.2%, the anti-V3 Ab response was assessed. Vaccinees' V3 Abs were highly cross-reactive with cyclic V3 peptides (cV3s) from diverse virus subtypes. Sieve analysis of CRF01_AE breakthrough viruses from 43 vaccine- and 66 placebo-recipients demonstrated an estimated vaccine efficacy of 85% against viruses with amino acids mismatching the vaccine at V3 site 317 (p = 0.004) and 52% against viruses matching the vaccine at V3 site 307 (p = 0.004). This analysis was supported by data showing that vaccinees' plasma Abs were less reactive with I307 when replaced with residues found more often in vaccinees' breakthrough viruses. Simultaneously, viruses with mutations at F317 were less infectious, possibly due to the contribution of F317 to optimal formation of the V3 hydrophobic core. These data suggest that RV144-induced V3-specific Abs imposed immune pressure on infecting viruses and inform efforts to design an HIV vaccine.
- Published
- 2014
- Full Text
- View/download PDF
5. CD8 and CD4 epitope predictions in RV144: no strong evidence of a T-cell driven sieve effect in HIV-1 breakthrough sequences from trial participants.
- Author
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Kalpana Dommaraju, Gustavo Kijak, Jonathan M Carlson, Brendan B Larsen, Sodsai Tovanabutra, Dan E Geraghty, Wenjie Deng, Brandon S Maust, Paul T Edlefsen, Eric Sanders-Buell, Silvia Ratto-Kim, Mark S deSouza, Supachai Rerks-Ngarm, Sorachai Nitayaphan, Punnee Pitisuttihum, Jaranit Kaewkungwal, Robert J O'Connell, Merlin L Robb, Nelson L Michael, James I Mullins, Jerome H Kim, and Morgane Rolland
- Subjects
Medicine ,Science - Abstract
The modest protection afforded by the RV144 vaccine offers an opportunity to evaluate its mechanisms of protection. Differences between HIV-1 breakthrough viruses from vaccine and placebo recipients can be attributed to the RV144 vaccine as this was a randomized and double-blinded trial. CD8 and CD4 T cell epitope repertoires were predicted in HIV-1 proteomes from 110 RV144 participants. Predicted Gag epitope repertoires were smaller in vaccine than in placebo recipients (p = 0.019). After comparing participant-derived epitopes to corresponding epitopes in the RV144 vaccine, the proportion of epitopes that could be matched differed depending on the protein conservation (only 36% of epitopes in Env vs 84-91% in Gag/Pol/Nef for CD8 predicted epitopes) or on vaccine insert subtype (55% against CRF01_AE vs 7% against subtype B). To compare predicted epitopes to the vaccine, we analyzed predicted binding affinity and evolutionary distance measurements. Comparisons between the vaccine and placebo arm did not reveal robust evidence for a T cell driven sieve effect, although some differences were noted in Env-V2 (0.022≤p-value≤0.231). The paucity of CD8 T cell responses identified following RV144 vaccination, with no evidence for V2 specificity, considered together both with the association of decreased infection risk in RV 144 participants with V-specific antibody responses and a V2 sieve effect, lead us to hypothesize that this sieve effect was not T cell specific. Overall, our results did not reveal a strong differential impact of vaccine-induced T cell responses among breakthrough infections in RV144 participants.
- Published
- 2014
- Full Text
- View/download PDF
6. Human papillomavirus detection in cervical neoplasia attributed to 12 high-risk human papillomavirus genotypes by region
- Author
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Castellsague, X, Ault, KA, Bosch, FX, Brown, D, Cuzick, J, Ferris, DG, Joura, EA, Garland, SM, Giuliano, AR, Hernandez-Avila, M, Huh, W, Iversen, O-E, Kjaer, SK, Luna, J, Monsonego, J, Munoz, N, Myers, E, Paavonen, J, Pitisuttihum, P, Steben, M, Wheeler, CM, Perez, G, Saah, A, Luxembourg, A, Sings, HL, Velicer, C, Castellsague, X, Ault, KA, Bosch, FX, Brown, D, Cuzick, J, Ferris, DG, Joura, EA, Garland, SM, Giuliano, AR, Hernandez-Avila, M, Huh, W, Iversen, O-E, Kjaer, SK, Luna, J, Monsonego, J, Munoz, N, Myers, E, Paavonen, J, Pitisuttihum, P, Steben, M, Wheeler, CM, Perez, G, Saah, A, Luxembourg, A, Sings, HL, and Velicer, C
- Abstract
BACKGROUND: We estimated the proportion of cervical intraepithelial neoplasia (CIN) cases attributed to 14 HPV types, including quadrivalent (qHPV) (6/11/16/18) and 9-valent (9vHPV) (6/11/16/18/31/33/45/52/58) vaccine types, by region METHODS: Women ages 15-26 and 24-45 years from 5 regions were enrolled in qHPV vaccine clinical trials. Among 10,706 women (placebo arms), 1539 CIN1, 945 CIN2/3, and 24 adenocarcinoma in situ (AIS) cases were diagnosed by pathology panel consensus. RESULTS: Predominant HPV types were 16/51/52/56 (anogenital infection), 16/39/51/52/56 (CIN1), and 16/31/52/58 (CIN2/3). In regions with largest sample sizes, minimal regional variation was observed in 9vHPV type prevalence in CIN1 (~50%) and CIN2/3 (81-85%). Types 31/33/45/52/58 accounted for 25-30% of CIN1 in Latin America and Europe, but 14-18% in North America and Asia. Types 31/33/45/52/58 accounted for 33-38% of CIN2/3 in Latin America (younger women), Europe, and Asia, but 17-18% of CIN2/3 in Latin America (older women) and North America. Non-vaccine HPV types 35/39/51/56/59 had similar or higher prevalence than qHPV types in CIN1 and were attributed to 2-11% of CIN2/3. CONCLUSIONS: The 9vHPV vaccine could potentially prevent the majority of CIN1-3, irrespective of geographic region. Notwithstanding, non-vaccine types 35/39/51/56/59 may still be responsible for some CIN1, and to a lesser extent CIN2/3.
- Published
- 2016
7. Human papillomavirus detection in cervical neoplasia attributed to 12 high-risk human papillomavirus genotypes by region
- Author
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Castellsagué, Xavier, Ault, Kevin A., Bosch, F. Xavier, Brown, Darron, Cuzick, Jack, Ferris, Daron G., Joura, Elmar A., Garland, Suzanne M., Giuliano, Anna R, Hernandez-Avila, Mauricio, Huh, Warner, Iversen, Ole-Erik, Kjaer, Susanne K., Luna, Joaquin, Monsonego, Joseph, Muñoz, Nubia, Myers, Evan, Paavonen, Jorma, Pitisuttihum, Punnee, Steben, Marc, Wheeler, Cosette M., Perez, Gonzalo, Saah, Alfred, Luxembourg, Alain, Sings, Heather L, and Velicer, Christine
- Abstract
We estimated the proportion of cervical intraepithelial neoplasia (CIN) cases attributed to 14 HPV types, including quadrivalent (qHPV) (6/11/16/18) and 9-valent (9vHPV) (6/11/16/18/31/33/45/52/58) vaccine types, by region
- Published
- 2016
- Full Text
- View/download PDF
8. Herpes Zoster (HZ) and Post-herpetic Neuralgia (PHN): Burden of Illness, Healthcare Utilization, and Costs; the Thai Perspective
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Pitisuttihum, P., primary
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- 2008
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9. Adenovirus-based HIV-1 vaccine candidates tested in efficacy trials elicit CD8+T cells with limited breadth of HIV-1 inhibition
- Author
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Hayes, Peter J., Cox, Josephine H., Coleman, Adam R., Fernandez, Natalia, Bergin, Philip J., Kopycinski, Jakub T., Nitayaphan, Sorachai, Pitisuttihum, Punnee, de Souza, Mark, Duerr, Ann, Morgan, Cecilia, and Gilmour, Jill W.
- Abstract
Supplemental Digital Content is available in the text
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- 2016
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10. Letter to the Editor on: The RV144 vaccine regimen was not associated with enhancement of infection
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Vasan, Sandhya, Rerks-Ngarm, Supachai, Gilbert, Peter, Haynes, Barton, Nitayapan, Sorachai, Pitisuttihum, Punnee, Kaewkungwal, Jaranit, Excler, Jean-Louis, Robb, Merlin, Michael, Nelson, Kim, Jerome, and O’Connell, Robert
- Published
- 2015
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11. Correction: RV144 HIV-1 vaccination impacts post-infection antibody responses.
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Mdluli T, Jian N, Slike B, Paquin-Proulx D, Donofrio G, Alrubayyi A, Gift S, Grande R, Bryson M, Lee A, Dussupt V, Mendez-Rivera L, Sanders-Buell E, Chenine AL, Tran U, Li Y, Brown E, Edlefsen PT, O'Connell R, Gilbert P, Nitayaphan S, Pitisuttihum P, Rerks-Ngarm S, Robb ML, Gramzinski R, Alter G, Tovanabutra S, Georgiev IS, Ackerman ME, Polonis VR, Vasan S, Michael NL, Kim JH, Eller MA, Krebs SJ, and Rolland M
- Abstract
[This corrects the article DOI: 10.1371/journal.ppat.1009101.].
- Published
- 2021
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12. RV144 HIV-1 vaccination impacts post-infection antibody responses.
- Author
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Mdluli T, Jian N, Slike B, Paquin-Proulx D, Donofrio G, Alrubayyi A, Gift S, Grande R, Bryson M, Lee A, Dussupt V, Mendez-Riveria L, Sanders-Buell E, Chenine AL, Tran U, Li Y, Brown E, Edlefsen PT, O'Connell R, Gilbert P, Nitayaphan S, Pitisuttihum P, Rerks-Ngarm S, Robb ML, Gramzinski R, Alter G, Tovanabutra S, Georgiev IS, Ackerman ME, Polonis VR, Vasan S, Michael NL, Kim JH, Eller MA, Krebs SJ, and Rolland M
- Subjects
- Adult, Antibody Formation immunology, B-Lymphocytes immunology, Female, HIV Antibodies blood, HIV-1, Humans, Immunoglobulin G immunology, Male, Middle Aged, env Gene Products, Human Immunodeficiency Virus immunology, AIDS Vaccines immunology, HIV Antibodies immunology, HIV Infections immunology, HIV Infections prevention & control
- Abstract
The RV144 vaccine efficacy clinical trial showed a reduction in HIV-1 infections by 31%. Vaccine efficacy was associated with stronger binding antibody responses to the HIV Envelope (Env) V1V2 region, with decreased efficacy as responses wane. High levels of Ab-dependent cellular cytotoxicity (ADCC) together with low plasma levels of Env-specific IgA also correlated with decreased infection risk. We investigated whether B cell priming from RV144 vaccination impacted functional antibody responses to HIV-1 following infection. Antibody responses were assessed in 37 vaccine and 63 placebo recipients at 6, 12, and 36 months following HIV diagnosis. The magnitude, specificity, dynamics, subclass recognition and distribution of the binding antibody response following infection were different in RV144 vaccine recipients compared to placebo recipients. Vaccine recipients demonstrated increased IgG1 binding specifically to V1V2, as well as increased IgG2 and IgG4 but decreased IgG3 to HIV-1 Env. No difference in IgA binding to HIV-1 Env was detected between the vaccine and placebo recipients following infection. RV144 vaccination limited the development of broadly neutralizing antibodies post-infection, but enhanced Fc-mediated effector functions indicating B cell priming by RV144 vaccination impacted downstream antibody function. However, these functional responses were not associated with clinical markers of disease progression. These data reveal that RV144 vaccination primed B cells towards specific binding and functional antibody responses following HIV-1 infection., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2020
- Full Text
- View/download PDF
13. Human Papillomavirus Genotypes From Vaginal and Vulvar Intraepithelial Neoplasia in Females 15-26 Years of Age.
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Garland SM, Joura EA, Ault KA, Bosch FX, Brown DR, Castellsagué X, Ferenczy A, Ferris DG, Giuliano AR, Hernandez-Avila M, Huh WK, Iversen OE, Kjaer SK, Kurman RJ, Luna J, Monsonego J, Muñoz N, Paavonen J, Pitisuttihum P, Ronnett BM, Steben M, Stoler MH, Wheeler CM, Wiley DJ, Perez G, Saah AJ, Luxembourg A, Li S, DiNubile MJ, Wagner M, and Velicer C
- Subjects
- Adolescent, Adult, Carcinoma in Situ epidemiology, Female, Humans, Papillomaviridae classification, Papillomavirus Infections complications, Papillomavirus Infections prevention & control, Papillomavirus Vaccines, Placebos, Uterine Cervical Neoplasms virology, Vaginal Neoplasms epidemiology, Vulvar Neoplasms epidemiology, Young Adult, Carcinoma in Situ virology, Genotype, Papillomaviridae genetics, Papillomavirus Infections virology, Vaginal Neoplasms virology, Vulvar Neoplasms virology
- Abstract
Objective: To estimate the proportion of vulvar and vaginal low-grade and high-grade squamous intraepithelial lesions (LSILs and HSILs) in females 15-26 years of age attributable to 14 human papillomavirus (HPV) genotypes (6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59)., Methods: A post hoc analysis of prospectively diagnosed vulvar and vaginal LSILs and HSILs among females 15-26 years of age enrolled in the placebo arms of two phase 3, randomized HPV vaccine trials assessed 14 prespecified HPV genotypes associated with cervical cancers or anogenital warts using a type-specific multiplex polymerase chain reaction assay. The frequency of lesions associated with specific HPV genotypes was estimated by proportional and other attribution methods., Results: During approximately 4 years of follow-up in 8,798 females, 40 vulvar LSILs and 46 vulvar HSILs were diagnosed in 68 females, and 118 vaginal LSILs and 33 vaginal HSILs were diagnosed in 107 females. Females developing vulvar (41.2%) or vaginal (49.5%) lesions also had cervical lesions, whereas 6.5% of females with cervical lesions had vaginal or vulvar lesions. At least 1 of the 14 HPV genotypes was detected in females with vulvar LSIL (72.5%), vulvar HSIL (91.3%), vaginal LSIL (61.9%), and vaginal HSIL (72.7%). Considering only HPV-positive lesions, the nine most common genotypes causing cervical cancer and anogenital warts (6, 11, 16, 18, 31, 33, 45, 52, and 58) were found in 89.4% of vulvar LSILs, 100% of vulvar HSILs, 56.0% of vaginal LSILs, and 78.3% of vaginal HSILs., Conclusion: Most vulvar and vaginal lesions were attributable to at least 1 of the 14 HPV genotypes analyzed. Effective immunization programs could potentially prevent substantial numbers of HPV-related vulvar and vaginal LSILs and HSILs., Clinical Trial Registration: CLINICALTRIALS.GOV,: NCT00092521 and NCT00092534.
- Published
- 2018
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14. Adenovirus-based HIV-1 vaccine candidates tested in efficacy trials elicit CD8+ T cells with limited breadth of HIV-1 inhibition.
- Author
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Hayes PJ, Cox JH, Coleman AR, Fernandez N, Bergin PJ, Kopycinski JT, Nitayaphan S, Pitisuttihum P, de Souza M, Duerr A, Morgan C, and Gilmour JW
- Subjects
- AIDS Vaccines administration & dosage, AIDS Vaccines genetics, CD4-Positive T-Lymphocytes virology, Cells, Cultured, Enzyme-Linked Immunospot Assay, Healthy Volunteers, Humans, Interferon-gamma metabolism, Vaccines, Synthetic administration & dosage, Vaccines, Synthetic genetics, Vaccines, Synthetic immunology, AIDS Vaccines immunology, Adenoviruses, Human genetics, CD8-Positive T-Lymphocytes immunology, Drug Carriers, HIV Infections prevention & control, HIV Infections therapy, HIV-1 immunology
- Abstract
Objectives: The ability of HIV-1 vaccine candidates MRKAd5, VRC DNA/Ad5 and ALVAC/AIDSVAX to elicit CD8 T cells with direct antiviral function was assessed and compared with HIV-1-infected volunteers., Design: Adenovirus serotype 5 (Ad5)-based regimens MRKAd5 and VRC DNA/Ad5, designed to elicit HIV-1-specific T cells, are immunogenic but failed to prevent infection or impact on viral loads in volunteers infected subsequently. Failure may be due in part to a lack of CD8 T cells with effective antiviral functions., Methods: An in-vitro viral inhibition assay tested the ability of bispecific antibody expanded CD8 T cells from peripheral blood mononuclear cells to inhibit replication of a multiclade panel of HIV-1 isolates in autologous CD4 T cells. HIV-1 proteins recognized by CD8 T cells were assessed by IFNγ enzyme-linked immunospot assay., Results: Ad5-based regimens elicited CD8 T cells that inhibited replication of HIV-1 IIIB isolate with more limited inhibition of other isolates. IIIB isolate Gag and Pol genes have high sequence identities (>96%) to vector HIV-1 gene inserts, and these were the predominant HIV-1 proteins recognized by CD8 T cells. Virus inhibition breadth was greater in antiretroviral naïve HIV-1-infected volunteers naturally controlling viremia (plasma viral load < 10 000/ml). HIV-1-inhibitory CD8 T cells were not elicited by the ALVAC/AIDSVAX regimen., Conclusion: The Ad5-based regimens, although immunogenic, elicited CD8 T cells with limited HIV-1-inhibition breadth. Effective T-cell-based vaccines should presumably elicit broader HIV-1-inhibition profiles. The viral inhibition assay can be used in vaccine design and to prioritize promising candidates with greater inhibition breadth for further clinical trials.
- Published
- 2016
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15. HIV-1 infections with multiple founders are associated with higher viral loads than infections with single founders.
- Author
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Janes H, Herbeck JT, Tovanabutra S, Thomas R, Frahm N, Duerr A, Hural J, Corey L, Self SG, Buchbinder SP, McElrath MJ, O'Connell RJ, Paris RM, Rerks-Ngarm S, Nitayaphan S, Pitisuttihum P, Kaewkungwal J, Robb ML, Michael NL, Mullins JI, Kim JH, Gilbert PB, and Rolland M
- Subjects
- HIV Infections virology, Humans, Founder Effect, HIV Infections genetics, HIV-1 isolation & purification, Viral Load
- Abstract
Given the variation in the HIV-1 viral load (VL) set point across subjects, as opposed to a fairly stable VL over time within an infected individual, it is important to identify the characteristics of the host and virus that affect VL set point. Although recently infected individuals with multiple phylogenetically linked HIV-1 founder variants represent a minority of HIV-1 infections, we found--n two different cohorts--hat more diverse HIV-1 populations in early infection were associated with significantly higher VL 1 year after HIV-1 diagnosis.
- Published
- 2015
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16. Vaccine-induced Human Antibodies Specific for the Third Variable Region of HIV-1 gp120 Impose Immune Pressure on Infecting Viruses.
- Author
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Zolla-Pazner S, Edlefsen PT, Rolland M, Kong XP, deCamp A, Gottardo R, Williams C, Tovanabutra S, Sharpe-Cohen S, Mullins JI, deSouza MS, Karasavvas N, Nitayaphan S, Rerks-Ngarm S, Pitisuttihum P, Kaewkungwal J, O'Connell RJ, Robb ML, Michael NL, Kim JH, and Gilbert P
- Abstract
To evaluate the role of V3-specific IgG antibodies (Abs) in the RV144 clinical HIV vaccine trial, which reduced HIV-1 infection by 31.2%, the anti-V3 Ab response was assessed. Vaccinees' V3 Abs were highly cross-reactive with cyclic V3 peptides (cV3s) from diverse virus subtypes. Sieve analysis of CRF01_AE breakthrough viruses from 43 vaccine- and 66 placebo-recipients demonstrated an estimated vaccine efficacy of 85% against viruses with amino acids mismatching the vaccine at V3 site 317 (p=0.004) and 52% against viruses matching the vaccine at V3 site 307 (p=0.004). This analysis was supported by data showing vaccinees' plasma Abs were less reactive with I
307 replaced with residues found more often in vaccinees' breakthrough viruses. Simultaneously, viruses with mutations at F317 were less infectious, possibly due to the contribution of F317 to optimal formation of the V3 hydrophobic core. These data suggest that RV144-induced V3-specific Abs imposed immune pressure on infecting viruses and inform efforts to design an HIV vaccine.- Published
- 2014
- Full Text
- View/download PDF
17. CD8 and CD4 epitope predictions in RV144: no strong evidence of a T-cell driven sieve effect in HIV-1 breakthrough sequences from trial participants.
- Author
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Dommaraju K, Kijak G, Carlson JM, Larsen BB, Tovanabutra S, Geraghty DE, Deng W, Maust BS, Edlefsen PT, Sanders-Buell E, Ratto-Kim S, deSouza MS, Rerks-Ngarm S, Nitayaphan S, Pitisuttihum P, Kaewkungwal J, O'Connell RJ, Robb ML, Michael NL, Mullins JI, Kim JH, and Rolland M
- Subjects
- Adolescent, Adult, Alleles, Epitopes, T-Lymphocyte chemistry, Female, Genotype, HIV Envelope Protein gp120 chemistry, HLA Antigens chemistry, Humans, Male, Proteome chemistry, Young Adult, gag Gene Products, Human Immunodeficiency Virus chemistry, AIDS Vaccines therapeutic use, CD4-Positive T-Lymphocytes cytology, CD8-Positive T-Lymphocytes cytology, HIV Infections prevention & control, HIV-1 genetics, Thioglycolates chemistry, Thiophenes chemistry
- Abstract
The modest protection afforded by the RV144 vaccine offers an opportunity to evaluate its mechanisms of protection. Differences between HIV-1 breakthrough viruses from vaccine and placebo recipients can be attributed to the RV144 vaccine as this was a randomized and double-blinded trial. CD8 and CD4 T cell epitope repertoires were predicted in HIV-1 proteomes from 110 RV144 participants. Predicted Gag epitope repertoires were smaller in vaccine than in placebo recipients (p = 0.019). After comparing participant-derived epitopes to corresponding epitopes in the RV144 vaccine, the proportion of epitopes that could be matched differed depending on the protein conservation (only 36% of epitopes in Env vs 84-91% in Gag/Pol/Nef for CD8 predicted epitopes) or on vaccine insert subtype (55% against CRF01_AE vs 7% against subtype B). To compare predicted epitopes to the vaccine, we analyzed predicted binding affinity and evolutionary distance measurements. Comparisons between the vaccine and placebo arm did not reveal robust evidence for a T cell driven sieve effect, although some differences were noted in Env-V2 (0.022≤p-value≤0.231). The paucity of CD8 T cell responses identified following RV144 vaccination, with no evidence for V2 specificity, considered together both with the association of decreased infection risk in RV 144 participants with V-specific antibody responses and a V2 sieve effect, lead us to hypothesize that this sieve effect was not T cell specific. Overall, our results did not reveal a strong differential impact of vaccine-induced T cell responses among breakthrough infections in RV144 participants.
- Published
- 2014
- Full Text
- View/download PDF
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