Rapid Induction of Multifunctional Antibodies in Rabbits and Macaques by Clade C HIV-1 CAP257 Envelopes Circulating During Epitope-Specific Neutralization Breadth Development
We report here on HIV-1 immunization results in rabbits and macaques co-immunized with clade C gp160 DNA and gp140 trimeric envelope vaccines, a strategy similar to a recent clinical trial that showed improved speed and magnitude of humoral responses. Clade C envelopes were isolated from CAP257, an...
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Frontiers Media S.A.
2020-06-01
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Series: | Frontiers in Immunology |
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Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00984/full |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Delphine C. Malherbe Constantinos Kurt Wibmer Molati Nonyane Jason Reed D. Noah Sather David A. Spencer Jason T. Schuman Biwei Guo Shilpi Pandey Harlan Robins Byung Park Deborah H. Fuller Jonah B. Sacha Penny L. Moore Penny L. Moore Penny L. Moore Penny L. Moore Ann J. Hessell Nancy L. Haigwood Nancy L. Haigwood |
spellingShingle |
Delphine C. Malherbe Constantinos Kurt Wibmer Molati Nonyane Jason Reed D. Noah Sather David A. Spencer Jason T. Schuman Biwei Guo Shilpi Pandey Harlan Robins Byung Park Deborah H. Fuller Jonah B. Sacha Penny L. Moore Penny L. Moore Penny L. Moore Penny L. Moore Ann J. Hessell Nancy L. Haigwood Nancy L. Haigwood Rapid Induction of Multifunctional Antibodies in Rabbits and Macaques by Clade C HIV-1 CAP257 Envelopes Circulating During Epitope-Specific Neutralization Breadth Development Frontiers in Immunology HIV vaccine envelope immunogen rabbit NHP neutralizing antibodies co-immunization |
author_facet |
Delphine C. Malherbe Constantinos Kurt Wibmer Molati Nonyane Jason Reed D. Noah Sather David A. Spencer Jason T. Schuman Biwei Guo Shilpi Pandey Harlan Robins Byung Park Deborah H. Fuller Jonah B. Sacha Penny L. Moore Penny L. Moore Penny L. Moore Penny L. Moore Ann J. Hessell Nancy L. Haigwood Nancy L. Haigwood |
author_sort |
Delphine C. Malherbe |
title |
Rapid Induction of Multifunctional Antibodies in Rabbits and Macaques by Clade C HIV-1 CAP257 Envelopes Circulating During Epitope-Specific Neutralization Breadth Development |
title_short |
Rapid Induction of Multifunctional Antibodies in Rabbits and Macaques by Clade C HIV-1 CAP257 Envelopes Circulating During Epitope-Specific Neutralization Breadth Development |
title_full |
Rapid Induction of Multifunctional Antibodies in Rabbits and Macaques by Clade C HIV-1 CAP257 Envelopes Circulating During Epitope-Specific Neutralization Breadth Development |
title_fullStr |
Rapid Induction of Multifunctional Antibodies in Rabbits and Macaques by Clade C HIV-1 CAP257 Envelopes Circulating During Epitope-Specific Neutralization Breadth Development |
title_full_unstemmed |
Rapid Induction of Multifunctional Antibodies in Rabbits and Macaques by Clade C HIV-1 CAP257 Envelopes Circulating During Epitope-Specific Neutralization Breadth Development |
title_sort |
rapid induction of multifunctional antibodies in rabbits and macaques by clade c hiv-1 cap257 envelopes circulating during epitope-specific neutralization breadth development |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2020-06-01 |
description |
We report here on HIV-1 immunization results in rabbits and macaques co-immunized with clade C gp160 DNA and gp140 trimeric envelope vaccines, a strategy similar to a recent clinical trial that showed improved speed and magnitude of humoral responses. Clade C envelopes were isolated from CAP257, an individual who developed a unique temporal pattern of neutralization breadth development, comprising three separate “Waves” targeting distinct Env epitopes and different HIV clades. We used phylogeny and neutralization criteria to down-select envelope vaccine candidates, and confirmed antigenicity of our antigens by interaction with well-characterized broadly neutralizing monoclonal antibodies. Using these envelopes, we performed rabbit studies that screened for immunogenicity of CAP257 Envs from timepoints preceding peak neutralization breadth in each Wave. Selected CAP257 envelopes from Waves 1 and 2, during the first 2 years of infection that were highly immunogenic in rabbits were then tested in macaques. We found that in rabbits and macaques, co-immunization of DNA, and protein envelope-based vaccines induced maximum binding and neutralizing antibody titers with three immunizations. No further benefit was obtained with additional immunizations. The vaccine strategies recapitulated the Wave-specific epitope targeting observed in the CAP257 participant, and elicited Tier 1A, 1B, and Tier 2 heterologous neutralization. CAP257 envelope immunogens also induced the development of ADCC and TFH responses in macaques, and these responses positively correlated with heterologous neutralization. Together, the results from two animal models in this study have implications for identifying effective vaccine immunogens. We used a multi-step strategy to (1) select an Env donor with well-characterized neutralization breadth development; (2) study Env phylogeny for potential immunogens circulating near peak breadth timepoints during the first 2 years of infection; (3) test down-selected Envs for antigenicity; (4) screen down-selected Envs in an effective vaccine regimen in rabbits; and (5) advance the most immunogenic Envs to NHP studies. The results were an induction of high titers of HIV-1 envelope-specific antibodies with increasing avidity and cross-clade neutralizing antibodies with effector functions that together may improve the potential for protection in a pre-clinical SHIV model. |
topic |
HIV vaccine envelope immunogen rabbit NHP neutralizing antibodies co-immunization |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2020.00984/full |
work_keys_str_mv |
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doaj-d97512fa6df54775844c17a2489a0df52020-11-25T03:31:55ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-06-011110.3389/fimmu.2020.00984536760Rapid Induction of Multifunctional Antibodies in Rabbits and Macaques by Clade C HIV-1 CAP257 Envelopes Circulating During Epitope-Specific Neutralization Breadth DevelopmentDelphine C. Malherbe0Constantinos Kurt Wibmer1Molati Nonyane2Jason Reed3D. Noah Sather4David A. Spencer5Jason T. Schuman6Biwei Guo7Shilpi Pandey8Harlan Robins9Byung Park10Deborah H. Fuller11Jonah B. Sacha12Penny L. Moore13Penny L. Moore14Penny L. Moore15Penny L. Moore16Ann J. Hessell17Nancy L. Haigwood18Nancy L. Haigwood19Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United StatesCentre for HIV and STIs, National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South AfricaCentre for HIV and STIs, National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South AfricaVaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, United StatesCenter for Global Infectious Disease Center, Seattle Children's Hospital Research Foundation, Seattle, WA, United StatesOregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United StatesBruker Daltonics, Portland, OR, United StatesOregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United StatesOregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United StatesFred Hutchinson Cancer Research Center, Seattle, WA, United StatesBiostatistics Unit, Primate Genetic Program Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United StatesAIDS Division, Department of Microbiology, Washington National Primate Research Center, University of Washington, Seattle, WA, United StatesVaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, United StatesCentre for HIV and STIs, National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South AfricaAntibody Immunity Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa0Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa1Division of Medical Virology, Department of Pathology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South AfricaOregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United StatesOregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United States2Molecular Microbiology and Immunology, School of Medicine, Oregon Health and Science University, Portland, OR, United StatesWe report here on HIV-1 immunization results in rabbits and macaques co-immunized with clade C gp160 DNA and gp140 trimeric envelope vaccines, a strategy similar to a recent clinical trial that showed improved speed and magnitude of humoral responses. Clade C envelopes were isolated from CAP257, an individual who developed a unique temporal pattern of neutralization breadth development, comprising three separate “Waves” targeting distinct Env epitopes and different HIV clades. We used phylogeny and neutralization criteria to down-select envelope vaccine candidates, and confirmed antigenicity of our antigens by interaction with well-characterized broadly neutralizing monoclonal antibodies. Using these envelopes, we performed rabbit studies that screened for immunogenicity of CAP257 Envs from timepoints preceding peak neutralization breadth in each Wave. Selected CAP257 envelopes from Waves 1 and 2, during the first 2 years of infection that were highly immunogenic in rabbits were then tested in macaques. We found that in rabbits and macaques, co-immunization of DNA, and protein envelope-based vaccines induced maximum binding and neutralizing antibody titers with three immunizations. No further benefit was obtained with additional immunizations. The vaccine strategies recapitulated the Wave-specific epitope targeting observed in the CAP257 participant, and elicited Tier 1A, 1B, and Tier 2 heterologous neutralization. CAP257 envelope immunogens also induced the development of ADCC and TFH responses in macaques, and these responses positively correlated with heterologous neutralization. Together, the results from two animal models in this study have implications for identifying effective vaccine immunogens. We used a multi-step strategy to (1) select an Env donor with well-characterized neutralization breadth development; (2) study Env phylogeny for potential immunogens circulating near peak breadth timepoints during the first 2 years of infection; (3) test down-selected Envs for antigenicity; (4) screen down-selected Envs in an effective vaccine regimen in rabbits; and (5) advance the most immunogenic Envs to NHP studies. The results were an induction of high titers of HIV-1 envelope-specific antibodies with increasing avidity and cross-clade neutralizing antibodies with effector functions that together may improve the potential for protection in a pre-clinical SHIV model.https://www.frontiersin.org/article/10.3389/fimmu.2020.00984/fullHIV vaccineenvelope immunogenrabbitNHPneutralizing antibodiesco-immunization |