Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting

PLoS Pathogens

Julie Overbaugh¹  James M. Binley²  Mark Connors³  Ivelin S. Georgiev⁴  Lynn Morris⁵  David C. Montefiori⁶  John R. Mascola⁶  Malcolm A. Martin⁷  Valerie Cortez⁸  Peter D. Kwong⁹  Rui Kong^1,10  Barton F. Haynes^1,11  Matthew S. Sutton^1,12  Mark K. Louder^1,12  Ryan S. Roark^1,12  Krisha McKee^1,12  Felicia Wang^1,12  Robert T. Bailer^1,12  Han R. Altae-Tran^1,12  Stephen D. Schmidt^1,12  Sijy O’Dell^1,12  Nicole A. Doria-Rose^1,12  Gwo-Yu Chuang^1,12  Salim S. Abdool Karim^1,13 

[1] Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham, NC, United States of America;Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa;Department of Epidemiology, Columbia University, New York, NY, United States of America;Department of Surgery, Duke University School of Medicine, Durham, NC, United States of America;Departments of Medicine and Immunology, Duke University School of Medicine, Durham, NC, United States of America;Duke University Human Vaccine Institute, Durham, NC, United States of America;HIV-Specific Immunity Section, National Institutes of Health, Bethesda, MD, United States of America;Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America;Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States of America;Program in Molecular and Cellular Biology, University of Washington, Seattle, WA, United States of America;San Diego Biomedical Research Institute, San Diego, CA, United States of America;Vaccine Research Center, National Institutes of Health, Bethesda, MD, United States of America;Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN, United States of America

关键词: Antibodies;    Antibody specificity;    Algorithms;    HIV-1;    Antibody response;    Monoclonal antibodies;    Simulation;    modeling;    Viral vaccines;   

DOI  :  10.1371/journal.ppat.1006148

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Computational neutralization fingerprinting, NFP, is an efficient and accurate method for predicting the epitope specificities of polyclonal antibody responses to HIV-1 infection. Here, we present next-generation NFP algorithms that substantially improve prediction accuracy for individual donors and enable serologic analysis for entire cohorts. Specifically, we developed algorithms for: (a) selection of optimized virus neutralization panels for NFP analysis, (b) estimation of NFP prediction confidence for each serum sample, and (c) identification of sera with potentially novel epitope specificities. At the individual donor level, the next-generation NFP algorithms particularly improved the ability to detect multiple epitope specificities in a sample, as confirmed both for computationally simulated polyclonal sera and for samples from HIV-infected donors. Specifically, the next-generation NFP algorithms detected multiple specificities in twice as many samples of simulated sera. Further, unlike the first-generation NFP, the new algorithms were able to detect both of the previously confirmed antibody specificities, VRC01-like and PG9-like, in donor CHAVI 0219. At the cohort level, analysis of ~150 broadly neutralizing HIV-infected donor samples suggested a potential connection between clade of infection and types of elicited epitope specificities. Most notably, while 10E8-like antibodies were observed in infections from different clades, an enrichment of such antibodies was predicted for clade B samples. Ultimately, such large-scale analyses of antibody responses to HIV-1 infection can help guide the design of epitope-specific vaccines that are tailored to take into account the prevalence of infecting clades within a specific geographic region. Overall, the next-generation NFP technology will be an important tool for the analysis of broadly neutralizing polyclonal antibody responses against HIV-1.

【 授权许可】

CC BY