title: Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting.
abstract: 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.
authors.affiliation: Vaccine Research Center, National Institutes of Health, Bethesda, MD, United States of America.
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Doria-Rose
authors.affiliation: Vaccine Research Center, National Institutes of Health, Bethesda, MD, United States of America.
authors.forename: Han R
authors.initials: HR
authors.lastname: Altae-Tran
authors.affiliation: Vaccine Research Center, National Institutes of Health, Bethesda, MD, United States of America.
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Roark
authors.affiliation: Vaccine Research Center, National Institutes of Health, Bethesda, MD, United States of America.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Schmidt
authors.affiliation: Vaccine Research Center, National Institutes of Health, Bethesda, MD, United States of America.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Sutton
authors.affiliation: Vaccine Research Center, National Institutes of Health, Bethesda, MD, United States of America.
authors.forename: Mark K
authors.initials: MK
authors.lastname: Louder
authors.affiliation: Vaccine Research Center, National Institutes of Health, Bethesda, MD, United States of America.
authors.forename: Gwo-Yu
authors.initials: GY
authors.lastname: Chuang
authors.affiliation: Vaccine Research Center, National Institutes of Health, Bethesda, MD, United States of America.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Bailer
authors.affiliation: Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America.|Program in Molecular and Cellular Biology, University of Washington, Seattle, WA, United States of America.
authors.forename: Valerie
authors.identifier: 0000-0002-1267-5596
authors.initials: V
authors.lastname: Cortez
authors.affiliation: Vaccine Research Center, National Institutes of Health, Bethesda, MD, United States of America.
authors.forename: Rui
authors.identifier: 0000-0003-1779-5885
authors.initials: R
authors.lastname: Kong
authors.affiliation: Vaccine Research Center, National Institutes of Health, Bethesda, MD, United States of America.
authors.forename: Krisha
authors.initials: K
authors.lastname: McKee
authors.affiliation: Vaccine Research Center, National Institutes of Health, Bethesda, MD, United States of America.
authors.forename: Sijy
authors.initials: S
authors.lastname: O'Dell
authors.affiliation: Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN, United States of America.
authors.forename: Felicia
authors.initials: F
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Salim S
authors.identifier: 0000-0002-4986-2133
authors.initials: SS
authors.lastname: Abdool Karim
authors.affiliation: San Diego Biomedical Research Institute, San Diego, CA, United States of America.
authors.forename: James M
authors.initials: JM
authors.lastname: Binley
authors.affiliation: HIV-Specific Immunity Section, National Institutes of Health, Bethesda, MD, United States of America.
authors.forename: Mark
authors.initials: M
authors.lastname: Connors
authors.affiliation: Duke University Human Vaccine Institute, Durham, NC, United States of America.|Departments of Medicine and Immunology, Duke University School of Medicine, Durham, NC, United States of America.|Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham, NC, United States of America.
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States of America.
authors.forename: Malcolm A
authors.identifier: 0000-0002-6845-9905
authors.initials: MA
authors.lastname: Martin
authors.affiliation: Duke University Human Vaccine Institute, Durham, NC, United States of America.|Department of Surgery, Duke University School of Medicine, Durham, NC, United States of America.
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.affiliation: Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa.|University of the Witwatersrand, Johannesburg, South Africa.|Center for HIV and STIs, National Institute for Communicable Diseases, Johannesburg, South Africa.
authors.forename: Lynn
authors.initials: L
authors.lastname: Morris
authors.affiliation: Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America.
authors.forename: Julie
authors.initials: J
authors.lastname: Overbaugh
authors.affiliation: Vaccine Research Center, National Institutes of Health, Bethesda, MD, United States of America.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Kwong
authors.affiliation: Vaccine Research Center, National Institutes of Health, Bethesda, MD, United States of America.
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.affiliation: Vaccine Research Center, National Institutes of Health, Bethesda, MD, United States of America.|Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN, United States of America.|Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, United States of America.|Department of Electrical Engineering and Computer Science, Vanderbilt University, Nashville, TN, United States of America.
authors.forename: Ivelin S
authors.initials: IS
authors.lastname: Georgiev
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000465:Algorithms; D000917:Antibody Formation; D000918:Antibody Specificity; D015331:Cohort Studies; D003198:Computer Simulation; D018604:Epitope Mapping / Q000379:methods*; D000939:Epitopes / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D009500:Neutralization Tests
chemical_list: D016915:AIDS Vaccines; D000939:Epitopes; D015483:HIV Antibodies