11 results on '"Corrigan, Angela R."'
Search Results
2. Soluble prefusion-closed HIV-envelope trimers with glycan-covered bases
- Author
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Olia, Adam S., Cheng, Cheng, Zhou, Tongqing, Biju, Andrea, Harris, Darcy R., Changela, Anita, Duan, Hongying, Ivleva, Vera B., Kong, Wing-Pui, Ou, Li, Rawi, Reda, Tsybovsky, Yaroslav, Van Wazer, David J., Corrigan, Angela R., Gonelli, Christopher A., Lee, Myungjin, McKee, Krisha, Narpala, Sandeep, O’Dell, Sijy, Parchment, Danealle K., Stancofski, Erik-Stephane D., Stephens, Tyler, Tan, Ivy, Teng, I-Ting, Wang, Shuishu, Wei, Qing, Yang, Yongping, Yang, Zhengrong, Zhang, Baoshan, Novak, Jan, Renfrow, Matthew B., Doria-Rose, Nicole A., Koup, Richard A., McDermott, Adrian B., Gall, Jason G., Lei, Q. Paula, Mascola, John R., and Kwong, Peter D.
- Published
- 2023
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3. Safety and immunogenicity of an HIV-1 prefusion-stabilized envelope trimer (Trimer 4571) vaccine in healthy adults: A first-in-human open-label, randomized, dose-escalation, phase 1 clinical trial
- Author
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Houser, Katherine V., Gaudinski, Martin R., Happe, Myra, Narpala, Sandeep, Verardi, Raffaello, Sarfo, Edward K., Corrigan, Angela R., Wu, Richard, Rothwell, Ro Shauna, Novik, Laura, Hendel, Cynthia S., Gordon, Ingelise J., Berkowitz, Nina M., Cartagena, Cora Trelles, Widge, Alicia T., Coates, Emily E., Strom, Larisa, Hickman, Somia, Conan-Cibotti, Michelle, Vazquez, Sandra, Trofymenko, Olga, Plummer, Sarah, Stein, Judy, Case, Christopher L., Nason, Martha, Biju, Andrea, Parchment, Danealle K., Changela, Anita, Cheng, Cheng, Duan, Hongying, Geng, Hui, Teng, I-Ting, Zhou, Tongqing, O'Connell, Sarah, Barry, Chris, Carlton, Kevin, Gall, Jason G., Flach, Britta, Doria-Rose, Nicole A., Graham, Barney S., Koup, Richard A., McDermott, Adrian B., Mascola, John R., Kwong, Peter D., and Ledgerwood, Julie E.
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- 2022
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4. Consistent elicitation of cross-clade HIV-neutralizing responses achieved in guinea pigs after fusion peptide priming by repetitive envelope trimer boosting.
- Author
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Cheng, Cheng, Xu, Kai, Kong, Rui, Chuang, Gwo-Yu, Corrigan, Angela R., Geng, Hui, Hill, Kurt R., Jafari, Alexander J., O’Dell, Sijy, Ou, Li, Rawi, Reda, Rowshan, Ariana P., Sarfo, Edward K., Sastry, Mallika, Saunders, Kevin O., Schmidt, Stephen D., Wang, Shuishu, Wu, Winston, Zhang, Baoshan, and Doria-Rose, Nicole A.
- Subjects
GUINEA pigs ,IMMUNIZATION ,ANTIBODY formation ,MONOCLONAL antibodies ,HIV - Abstract
The vaccine elicitation of broadly neutralizing responses is a central goal of HIV research. Recently, we elicited cross-clade neutralizing responses against the N terminus of the fusion peptide (FP), a critical component of the HIV-entry machinery. While the consistency of the elicited cross-clade neutralizing responses was good in mice, it was poor in guinea pigs: after seven immunizations comprising either envelope (Env) trimer or FP coupled to a carrier, serum from only one of five animals could neutralize a majority of a cross-clade panel of 19 wild-type strains. Such a low response rate—only 20%—made increasing consistency an imperative. Here, we show that additional Env-trimer immunizations could boost broad FP-directed neutralizing responses in a majority of immunized animals. The first boost involved a heterologous Env trimer developed from the transmitted founder clade C strain of donor CH505, and the second boost involved a cocktail that combined the CH505 trimer with a trimer from the BG505 strain. After boosting, sera from three of five animals neutralized a majority of the 19-strain panel and serum from a fourth animal neutralized 8 strains. We demonstrate that cross-reactive serum neutralization targeted the FP by blocking neutralization with soluble fusion peptide. The FP competition revealed two categories of elicited responses: an autologous response to the BG505 strain of high potency (~10,000 ID
50 ), which was not competed by soluble FP, and a heterologous response of lower potency, which was competed by soluble FP. While the autologous response could increase rapidly in response to Env-trimer boost, the heterologous neutralizing response increased more slowly. Overall, repetitive Env-trimer immunizations appeared to boost low titer FP-carrier primed responses to detectable levels, yielding cross-clade neutralization. The consistent trimer-boosted neutralizing responses described here add to accumulating evidence for the vaccine utility of the FP site of HIV vulnerability. [ABSTRACT FROM AUTHOR]- Published
- 2019
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- View/download PDF
5. Fusion peptide priming reduces immune responses to HIV-1 envelope trimer base.
- Author
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Corrigan, Angela R., Duan, Hongying, Cheng, Cheng, Gonelli, Christopher A., Ou, Li, Xu, Kai, DeMouth, Megan E., Geng, Hui, Narpala, Sandeep, O'Connell, Sarah, Zhang, Baoshan, Zhou, Tongqing, Basappa, Manjula, Boyington, Jeffrey C., Chen, Steven J., O'Dell, Sijy, Pegu, Amarendra, Stephens, Tyler, Tsybovsky, Yaroslav, and van Schooten, Jelle
- Abstract
Soluble "SOSIP"-stabilized envelope (Env) trimers are promising HIV-vaccine immunogens. However, they induce high-titer responses against the glycan-free trimer base, which is occluded on native virions. To delineate the effect on base responses of priming with immunogens targeting the fusion peptide (FP) site of vulnerability, here, we quantify the prevalence of trimer-base antibody responses in 49 non-human primates immunized with various SOSIP-stabilized Env trimers and FP-carrier conjugates. Trimer-base responses account for ∼90% of the overall trimer response in animals immunized with trimer only, ∼70% in animals immunized with a cocktail of SOSIP trimer and FP conjugate, and ∼30% in animals primed with FP conjugates before trimer immunization. Notably, neutralization breadth in FP-conjugate-primed animals correlates inversely with trimer-base responses. Our data provide methods to quantify the prevalence of trimer-base responses and reveal that FP-conjugate priming, either alone or as part of a cocktail, can reduce the trimer-base response and improve the neutralization outcome. [Display omitted] • Devise methods to quantify antibody responses targeting the base of HIV-1 Env trimers • Fusion-peptide (FP) priming reduces anti-base responses upon HIV Env trimer boost • Lower percentage of anti-base responses correlates with improved neutralization breadth The exposed base region of soluble HIV-1 Env trimers elicits strong non-neutralizing antibody responses. Corrigan et al. quantify plasma anti-base responses in immunized NHPs and observe a reduction in anti-base responses with fusion-peptide priming. The percentage of anti-base responses correlates inversely with neutralization breadth, providing insights for improving vaccination strategies. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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6. Immune Monitoring Reveals Fusion Peptide Priming to Imprint Cross-Clade HIV-Neutralizing Responses with a Characteristic Early B Cell Signature.
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Cheng, Cheng, Duan, Hongying, Xu, Kai, Chuang, Gwo-Yu, Corrigan, Angela R., Geng, Hui, O'Dell, Sijy, Ou, Li, Chambers, Michael, Changela, Anita, Chen, Xuejun, Foulds, Kathryn E., Sarfo, Edward K., Jafari, Alexander J., Hill, Kurt R., Kong, Rui, Liu, Kevin, Todd, John P., Tsybovsky, Yaroslav, and Verardi, Raffaello
- Abstract
The HIV fusion peptide (FP) is a promising vaccine target. FP-directed monoclonal antibodies from vaccinated macaques have been identified that neutralize up to ∼60% of HIV strains; these vaccinations, however, have involved ∼1 year with an extended neutralization-eclipse phase without measurable serum neutralization. Here, in 32 macaques, we test seven vaccination regimens, each comprising multiple immunizations of FP-carrier conjugates and HIV envelope (Env) trimers. Comparisons of vaccine regimens reveal FP-carrier conjugates to imprint cross-clade neutralizing responses and a cocktail of FP conjugate and Env trimer to elicit the earliest broad responses. We identify a signature, appearing as early as week 6 and involving the frequency of B cells recognizing both FP and Env trimer, predictive of vaccine-elicited breadth ∼1 year later. Immune monitoring of B cells in response to vaccination can thus enable vaccine insights even in the absence of serum neutralization, here identifying FP imprinting, cocktail approach, and early signature as means to improve FP-directed vaccine responses. • Immunization in 32 rhesus macaques reveals FP priming to imprint cross-clade responses • Identifying an early B cell signature predictive of vaccine outcome • Priming with a cocktail of FP and trimer elicits the earliest neutralizing responses • B cell immune monitoring enables vaccine insights, even without serum neutralization Immune monitoring of B cells in response to vaccination can enable early insights, even in the absence of serum neutralization. Cheng et al. observe an early B cell signature in NHPs predictive of the vaccine outcome, with priming of HIV FP imprinting cross-clade neutralizing FP-directed vaccine responses. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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7. Development of a 3Mut-Apex-Stabilized Envelope Trimer That Expands HIV-1 Neutralization Breadth When Used To Boost Fusion Peptide-Directed Vaccine-Elicited Responses.
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Gwo-Yu Chuang, Yen-Ting Lai, Boyington, Jeffrey C., Cheng Cheng, Hui Geng, Narpala, Sandeep, Rawi, Reda, Schmidt, Stephen D., Tsybovsky, Yaroslav, Verardi, Raffaello, Kai Xu, Yongping Yang, Baoshan Zhang, Chambers, Michael, Changela, Anita, Corrigan, Angela R., Rui Kong, Olia, Adam S., Li Ou, and Sarfo, Edward K.
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N-terminal residues , *DIHEDRAL angles , *VACCINE effectiveness , *GUINEA pigs , *VACCINE trials - Abstract
HIV-1 envelope (Env) trimers, stabilized in a prefusion-closed conformation, can elicit humoral responses capable of neutralizing HIV-1 strains closely matched in sequence to the immunizing strain. One strategy to increase elicited neutralization breadth involves vaccine priming of immune responses against a target site of vulnerability, followed by vaccine boosting of these responses with prefusion-closed Env trimers. This strategy has succeeded at the fusion peptide (FP) site of vulnerability in eliciting cross-clade neutralizing responses in standard vaccine-test animals. However, the breadth and potency of the elicited responses have been less than optimal. Here, we identify three mutations (3mut), Met302, Leu320, and Pro329, that stabilize the apex of the Env trimer in a prefusion-closed conformation and show antigenically, structurally, and immunogenically that combining 3mut with other approaches (e.g., repair and stabilize and glycine-helix breaking) yields well-behaved clade C-Env trimers capable of boosting the breadth of FPdirected responses. Crystal structures of these trimers confirmed prefusion-closed apexes stabilized by hydrophobic patches contributed by Met302 and Leu320, with Pro329 assuming canonically restricted dihedral angles. We substituted the N-terminal eight residues of FP (FP8, residues 512 to 519) of these trimers with the second most prevalent FP8 sequence (FP8v2, AVGLGAVF) and observed a 3mutstabilized consensus clade C-Env trimer with FP8v2 to boost the breadth elicited in guinea pigs of FP-directed responses induced by immunogens containing the most prevalent FP8 sequence (FP8v1, AVGIGAVF). Overall, 3mut can stabilize the Env trimer apex, and the resultant apex-stabilized Env trimers can be used to expand the neutralization breadth elicited against the FP site of vulnerability. IMPORTANCE A major hurdle to the development of an effective HIV-1 vaccine is the elicitation of serum responses capable of neutralizing circulating strains of HIV, which are extraordinarily diverse in sequence and often highly neutralization resistant. Recently, we showed how sera with 20 to 30% neutralization breadth could, nevertheless, be elicited in standard vaccine test animals by priming with the most prevalent N-terminal 8 residues of the HIV-1 fusion peptide (FP8), followed by boosting with a stabilized BG505-envelope (Env) trimer. Here, we show that subsequent boosting with a 3mut-apex-stabilized consensus C-Env trimer, modified to have the second most prevalent FP8 sequence, elicits higher neutralization breadth than that induced by continued boosting with the stabilized BG505-Env trimer. With increased neutralizing breadth elicited by boosting with a heterologous trimer containing the second most prevalent FP8 sequence, the fusion peptide-directed immune-focusing approach moves a step closer toward realizing an effective HIV-1 vaccine regimen. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
8. Diverse Murine Vaccinations Reveal Distinct Antibody Classes to Target Fusion Peptide and Variation in Peptide Length to Improve HIV Neutralization.
- Author
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Sastry M, Changela A, Gorman J, Xu K, Chuang GY, Shen CH, Cheng C, Geng H, O'Dell S, Ou L, Rawi R, Reveiz M, Stewart-Jones GBE, Wang S, Zhang B, Zhou T, Biju A, Chambers M, Chen X, Corrigan AR, Lin BC, Louder MK, McKee K, Nazzari AF, Olia AS, Parchment DK, Sarfo EK, Stephens T, Stuckey J, Tsybovsky Y, Verardi R, Wang Y, Zheng CY, Chen Y, Doria-Rose NA, McDermott AB, Mascola JR, and Kwong PD
- Subjects
- Animals, Guinea Pigs, Mice, HIV Antibodies, Immunoglobulin Isotypes, Vaccination, Peptides, Antibodies, Neutralizing, Broadly Neutralizing Antibodies, env Gene Products, Human Immunodeficiency Virus, HIV Seropositivity, AIDS Vaccines, HIV-1, HIV Infections prevention & control
- Abstract
While neutralizing antibodies that target the HIV-1 fusion peptide have been elicited in mice by vaccination, antibodies reported thus far have been from only a single antibody class that could neutralize ~30% of HIV-1 strains. To explore the ability of the murine immune system to generate cross-clade neutralizing antibodies and to investigate how higher breadth and potency might be achieved, we tested 17 prime-boost regimens that utilized diverse fusion peptide-carrier conjugates and HIV-1 envelope trimers with different fusion peptides. We observed priming in mice with fusion peptide-carrier conjugates of variable peptide length to elicit higher neutralizing responses, a result we confirmed in guinea pigs. From vaccinated mice, we isolated 21 antibodies, belonging to 4 distinct classes of fusion peptide-directed antibodies capable of cross-clade neutralization. Top antibodies from each class collectively neutralized over 50% of a 208-strain panel. Structural analyses - both X-ray and cryo-EM - revealed each antibody class to recognize a distinct conformation of fusion peptide and to have a binding pocket capable of accommodating diverse fusion peptides. Murine vaccinations can thus elicit diverse neutralizing antibodies, and altering peptide length during prime can improve the elicitation of cross-clade responses targeting the fusion peptide site of HIV-1 vulnerability. IMPORTANCE The HIV-1 fusion peptide has been identified as a site for elicitation of broadly neutralizing antibodies, with prior studies demonstrating that priming with fusion peptide-based immunogens and boosting with soluble envelope (Env) trimers can elicit cross-clade HIV-1-neutralizing responses. To improve the neutralizing breadth and potency of fusion peptide-directed responses, we evaluated vaccine regimens that incorporated diverse fusion peptide-conjugates and Env trimers with variation in fusion peptide length and sequence. We found that variation in peptide length during prime elicits enhanced neutralizing responses in mice and guinea pigs. We identified vaccine-elicited murine monoclonal antibodies from distinct classes capable of cross-clade neutralization and of diverse fusion peptide recognition. Our findings lend insight into improved immunogens and regimens for HIV-1 vaccine development., Competing Interests: The authors declare no conflict of interest.
- Published
- 2023
- Full Text
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9. Assessment of Crosslinkers between Peptide Antigen and Carrier Protein for Fusion Peptide-Directed Vaccines against HIV-1.
- Author
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Ou L, Gulla K, Biju A, Biner DW, Bylund T, Changela A, Chen SJ, Zheng CY, Cibelli N, Corrigan AR, Duan H, Gonelli CA, Kong WP, Cheng C, O'Dell S, Sarfo EK, Shaddeau A, Wang S, Vinitsky A, Yang Y, Zhang B, Zhang Y, Koup RA, Doria-Rose NA, Gall JG, Mascola JR, and Kwong PD
- Abstract
Conjugate-vaccine immunogens require three components: a carrier protein, an antigen, and a crosslinker, capable of coupling antigen to carrier protein, while preserving both T-cell responses from carrier protein and B-cell responses from antigen. We previously showed that the N-terminal eight residues of the HIV-1 fusion peptide (FP8) as an antigen could prime for broad cross-clade neutralizing responses, that recombinant heavy chain of tetanus toxin (rTTHC) as a carrier protein provided optimal responses, and that choice of crosslinker could impact both antigenicity and immunogenicity. Here, we delve more deeply into the impact of varying the linker between FP8 and rTTHC. In specific, we assessed the physical properties, the antigenicity, and the immunogenicity of conjugates for crosslinkers ranging in spacer-arm length from 1.5 to 95.2 Å, with varying hydrophobicity and crosslinking-functional groups. Conjugates coupled with different degrees of multimerization and peptide-to-rTTHC stoichiometry, but all were well recognized by HIV-fusion-peptide-directed antibodies VRC34.01, VRC34.05, PGT151, and ACS202 except for the conjugate with the longest linker (24-PEGylated SMCC; SM(PEG)24), which had lower affinity for ACS202, as did the conjugate with the shortest linker (succinimidyl iodoacetate; SIA), which also had the lowest peptide-to-rTTHC stoichiometry. Murine immunizations testing seven FP8-rTTHC conjugates elicited fusion-peptide-directed antibody responses, with SIA- and SM(PEG)24-linked conjugates eliciting lower responses than the other five conjugates. After boosting with prefusion-closed envelope trimers from strains BG505 clade A and consensus clade C, trimer-directed antibody-binding responses were lower for the SIA-linked conjugate; elicited neutralizing responses were similar, however, though statistically lower for the SM(PEG)24-linked conjugate, when tested against a strain especially sensitive to fusion-peptide-directed responses. Overall, correlation analyses revealed the immunogenicity of FP8-rTTHC conjugates to be negatively impacted by hydrophilicity and extremes of length or low peptide-carrier stoichiometry, but robust to other linker parameters, with several commonly used crosslinkers yielding statistically indistinguishable serological results.
- Published
- 2022
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10. Development of a 3Mut-Apex-Stabilized Envelope Trimer That Expands HIV-1 Neutralization Breadth When Used To Boost Fusion Peptide-Directed Vaccine-Elicited Responses.
- Author
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Chuang GY, Lai YT, Boyington JC, Cheng C, Geng H, Narpala S, Rawi R, Schmidt SD, Tsybovsky Y, Verardi R, Xu K, Yang Y, Zhang B, Chambers M, Changela A, Corrigan AR, Kong R, Olia AS, Ou L, Sarfo EK, Wang S, Wu W, Doria-Rose NA, McDermott AB, Mascola JR, and Kwong PD
- Subjects
- Animals, Antibodies, Neutralizing immunology, Female, Guinea Pigs, HEK293 Cells, HIV Antibodies immunology, HIV Seropositivity, HIV-1 immunology, Humans, Immunization, Secondary, Peptides, Vaccines, Subunit, AIDS Vaccines immunology, env Gene Products, Human Immunodeficiency Virus genetics, env Gene Products, Human Immunodeficiency Virus immunology
- Abstract
HIV-1 envelope (Env) trimers, stabilized in a prefusion-closed conformation, can elicit humoral responses capable of neutralizing HIV-1 strains closely matched in sequence to the immunizing strain. One strategy to increase elicited neutralization breadth involves vaccine priming of immune responses against a target site of vulnerability, followed by vaccine boosting of these responses with prefusion-closed Env trimers. This strategy has succeeded at the fusion peptide (FP) site of vulnerability in eliciting cross-clade neutralizing responses in standard vaccine-test animals. However, the breadth and potency of the elicited responses have been less than optimal. Here, we identify three mutations (3mut), Met302, Leu320, and Pro329, that stabilize the apex of the Env trimer in a prefusion-closed conformation and show antigenically, structurally, and immunogenically that combining 3mut with other approaches (e.g., repair and stabilize and glycine-helix breaking) yields well-behaved clade C-Env trimers capable of boosting the breadth of FP-directed responses. Crystal structures of these trimers confirmed prefusion-closed apexes stabilized by hydrophobic patches contributed by Met302 and Leu320, with Pro329 assuming canonically restricted dihedral angles. We substituted the N-terminal eight residues of FP (FP8, residues 512 to 519) of these trimers with the second most prevalent FP8 sequence (FP8v2, AVGLGAVF) and observed a 3mut-stabilized consensus clade C-Env trimer with FP8v2 to boost the breadth elicited in guinea pigs of FP-directed responses induced by immunogens containing the most prevalent FP8 sequence (FP8v1, AVGIGAVF). Overall, 3mut can stabilize the Env trimer apex, and the resultant apex-stabilized Env trimers can be used to expand the neutralization breadth elicited against the FP site of vulnerability. IMPORTANCE A major hurdle to the development of an effective HIV-1 vaccine is the elicitation of serum responses capable of neutralizing circulating strains of HIV, which are extraordinarily diverse in sequence and often highly neutralization resistant. Recently, we showed how sera with 20 to 30% neutralization breadth could, nevertheless, be elicited in standard vaccine test animals by priming with the most prevalent N-terminal 8 residues of the HIV-1 fusion peptide (FP8), followed by boosting with a stabilized BG505-envelope (Env) trimer. Here, we show that subsequent boosting with a 3mut-apex-stabilized consensus C-Env trimer, modified to have the second most prevalent FP8 sequence, elicits higher neutralization breadth than that induced by continued boosting with the stabilized BG505-Env trimer. With increased neutralizing breadth elicited by boosting with a heterologous trimer containing the second most prevalent FP8 sequence, the fusion peptide-directed immune-focusing approach moves a step closer toward realizing an effective HIV-1 vaccine regimen., (Copyright © 2020 American Society for Microbiology.)
- Published
- 2020
- Full Text
- View/download PDF
11. Antibody Lineages with Vaccine-Induced Antigen-Binding Hotspots Develop Broad HIV Neutralization.
- Author
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Kong R, Duan H, Sheng Z, Xu K, Acharya P, Chen X, Cheng C, Dingens AS, Gorman J, Sastry M, Shen CH, Zhang B, Zhou T, Chuang GY, Chao CW, Gu Y, Jafari AJ, Louder MK, O'Dell S, Rowshan AP, Viox EG, Wang Y, Choi CW, Corcoran MM, Corrigan AR, Dandey VP, Eng ET, Geng H, Foulds KE, Guo Y, Kwon YD, Lin B, Liu K, Mason RD, Nason MC, Ohr TY, Ou L, Rawi R, Sarfo EK, Schön A, Todd JP, Wang S, Wei H, Wu W, Mullikin JC, Bailer RT, Doria-Rose NA, Karlsson Hedestam GB, Scorpio DG, Overbaugh J, Bloom JD, Carragher B, Potter CS, Shapiro L, Kwong PD, and Mascola JR
- Subjects
- Amino Acid Sequence, Animals, Antibodies, Neutralizing chemistry, Antibodies, Neutralizing classification, B-Lymphocytes cytology, B-Lymphocytes metabolism, Crystallography, X-Ray, Female, HEK293 Cells, HIV Antibodies chemistry, HIV Antibodies classification, HIV-1 metabolism, Humans, Macaca mulatta, Male, Peptides chemistry, Protein Structure, Tertiary, env Gene Products, Human Immunodeficiency Virus chemistry, env Gene Products, Human Immunodeficiency Virus immunology, env Gene Products, Human Immunodeficiency Virus metabolism, AIDS Vaccines immunology, Antibodies, Neutralizing immunology, HIV Antibodies immunology, Peptides immunology
- Abstract
The vaccine-mediated elicitation of antibodies (Abs) capable of neutralizing diverse HIV-1 strains has been a long-standing goal. To understand how broadly neutralizing antibodies (bNAbs) can be elicited, we identified, characterized, and tracked five neutralizing Ab lineages targeting the HIV-1-fusion peptide (FP) in vaccinated macaques over time. Genetic and structural analyses revealed two of these lineages to belong to a reproducible class capable of neutralizing up to 59% of 208 diverse viral strains. B cell analysis indicated each of the five lineages to have been initiated and expanded by FP-carrier priming, with envelope (Env)-trimer boosts inducing cross-reactive neutralization. These Abs had binding-energy hotspots focused on FP, whereas several FP-directed Abs induced by immunization with Env trimer-only were less FP-focused and less broadly neutralizing. Priming with a conserved subregion, such as FP, can thus induce Abs with binding-energy hotspots coincident with the target subregion and capable of broad neutralization., (Published by Elsevier Inc.)
- Published
- 2019
- Full Text
- View/download PDF
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