HIV vaccine delayed boosting increases Env variable region 2-specific antibody effector functions

In the RV144 HIV-1 phase III trial, vaccine efficacy directly correlated with the magnitude of the variable region 2-specific (V2-specific) IgG antibody response, and in the presence of low plasma IgA levels, with the magnitude of plasma antibody-dependent cellular cytotoxicity. Reenrollment of RV14...

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Bibliographic Details
Published in:JCI insight 2020-01, Vol.5 (2)
Main Authors: Easterhoff, David, Pollara, Justin, Luo, Kan, Janus, Benjamin, Gohain, Neelakshi, Williams, LaTonya D, Tay, Matthew Zirui, Monroe, Anthony, Peachman, Kristina, Choe, Misook, Min, Susie, Lusso, Paolo, Zhang, Peng, Go, Eden P, Desaire, Heather, Bonsignori, Mattia, Hwang, Kwan-Ki, Beck, Charles, Kakalis, Matina, O'Connell, Robert J, Vasan, Sandhya, Kim, Jerome H, Michael, Nelson L, Excler, Jean-Louis, Robb, Merlin L, Rerks-Ngarm, Supachai, Kaewkungwal, Jaranit, Pitisuttithum, Punnee, Nitayaphan, Sorachai, Sinangil, Faruk, Tartaglia, James, Phogat, Sanjay, Wiehe, Kevin, Saunders, Kevin O, Montefiori, David C, Tomaras, Georgia D, Moody, M Anthony, Arthos, James, Rao, Mangala, Joyce, M Gordon, Ofek, Gilad, Ferrari, Guido, Haynes, Barton F
Format: Article
Language:English
Subjects:
AIDS Vaccines - chemistry
AIDS Vaccines - immunology
Antibodies, Monoclonal - chemistry
Antibodies, Monoclonal - genetics
Antibodies, Monoclonal - immunology
Antibody-Dependent Cell Cytotoxicity
Clinical Trials as Topic
env Gene Products, Human Immunodeficiency Virus - genetics
env Gene Products, Human Immunodeficiency Virus - immunology
Epitopes - genetics
Epitopes - immunology
HIV Antibodies - chemistry
HIV Antibodies - genetics
HIV Antibodies - immunology
HIV Infections - immunology
HIV Infections - prevention & control
HIV-1 - immunology
Humans
Immunization, Secondary
Immunoglobulin Variable Region - genetics
Immunoglobulin Variable Region - immunology
Models, Molecular
Mutation
Protein Conformation
Viral Vaccines
X-Ray Diffraction
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Summary:In the RV144 HIV-1 phase III trial, vaccine efficacy directly correlated with the magnitude of the variable region 2-specific (V2-specific) IgG antibody response, and in the presence of low plasma IgA levels, with the magnitude of plasma antibody-dependent cellular cytotoxicity. Reenrollment of RV144 vaccinees in the RV305 trial offered the opportunity to define the function, maturation, and persistence of vaccine-induced V2-specific and other mAb responses after boosting. We show that the RV144 vaccine regimen induced persistent V2 and other HIV-1 envelope-specific memory B cell clonal lineages that could be identified throughout the approximately 11-year vaccination period. Subsequent boosts increased somatic hypermutation, a critical requirement for antibody affinity maturation. Characterization of 22 vaccine-induced V2-specific mAbs with epitope specificities distinct from previously characterized RV144 V2-specific mAbs CH58 and CH59 found increased in vitro antibody-mediated effector functions. Thus, when inducing non-neutralizing antibodies, one method by which to improve HIV-1 vaccine efficacy may be through late boosting to diversify the V2-specific response to increase the breadth of antibody-mediated anti-HIV-1 effector functions.
ISSN:2379-3708
2379-3708
DOI:10.1172/jci.insight.131437