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

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...

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Published inPLoS pathogens Vol. 13; no. 1; p. e1006148
Main Authors Doria-Rose, Nicole A., Altae-Tran, Han R., Roark, Ryan S., Schmidt, Stephen D., Sutton, Matthew S., Louder, Mark K., Chuang, Gwo-Yu, Bailer, Robert T., Cortez, Valerie, Kong, Rui, McKee, Krisha, O’Dell, Sijy, Wang, Felicia, Abdool Karim, Salim S., Binley, James M., Connors, Mark, Haynes, Barton F., Martin, Malcolm A., Montefiori, David C., Morris, Lynn, Overbaugh, Julie, Kwong, Peter D., Mascola, John R., Georgiev, Ivelin S.
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 01.01.2017
Public Library of Science (PLoS)
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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.
AbstractList   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.
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.
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. HIV-1 remains a significant global health threat, with no effective vaccine against the virus currently available. Since traditional vaccine design efforts have had limited success, much effort in recent years has focused on gaining a better understanding of the ways select individuals are able to effectively neutralize the virus upon natural infection, and to utilize that knowledge for the design of optimized vaccine candidates. Primary emphasis has been placed on characterizing the antibody arm of the immune system, and specifically on antibodies capable of neutralizing the majority of circulating HIV-1 strains. Various experimental techniques can be applied to map the epitope targets of these antibodies, but more recently, the development of computational methods has provided an efficient and accurate alternative for understanding the complex antibody responses to HIV-1 in a given individual. Here, we present the next generation of this computational technology, and show that these new methods have significantly improved accuracy and confidence, and that they enable the interrogation of biologically important questions that can lead to new insights for the design of an effective vaccine against HIV-1.
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.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.
Audience Academic
Author Cortez, Valerie
O’Dell, Sijy
Connors, Mark
Morris, Lynn
Roark, Ryan S.
Wang, Felicia
Louder, Mark K.
Binley, James M.
Martin, Malcolm A.
Mascola, John R.
Sutton, Matthew S.
Kong, Rui
Abdool Karim, Salim S.
Kwong, Peter D.
Doria-Rose, Nicole A.
Altae-Tran, Han R.
Chuang, Gwo-Yu
Overbaugh, Julie
McKee, Krisha
Bailer, Robert T.
Montefiori, David C.
Schmidt, Stephen D.
Haynes, Barton F.
Georgiev, Ivelin S.
AuthorAffiliation 9 Duke University Human Vaccine Institute, Durham, NC, United States of America
12 Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States of America
University of Zurich, SWITZERLAND
11 Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham, NC, United States of America
6 Department of Epidemiology, Columbia University, New York, NY, United States of America
3 Program in Molecular and Cellular Biology, University of Washington, Seattle, WA, United States of America
13 Department of Surgery, Duke University School of Medicine, Durham, NC, United States of America
5 Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa
17 Department of Electrical Engineering and Computer Science, Vanderbilt University, Nashville, TN, United States of America
14 University of the Witwatersrand, Johannesburg, South Africa
8 HI
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/28052137$$D View this record in MEDLINE/PubMed
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ContentType Journal Article
Copyright COPYRIGHT 2017 Public Library of Science
2017 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Doria-Rose NA, Altae-Tran HR, Roark RS, Schmidt SD, Sutton MS, Louder MK, et al. (2017) Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting. PLoS Pathog 13(1): e1006148. doi:10.1371/journal.ppat.1006148
2017 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Doria-Rose NA, Altae-Tran HR, Roark RS, Schmidt SD, Sutton MS, Louder MK, et al. (2017) Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting. PLoS Pathog 13(1): e1006148. doi:10.1371/journal.ppat.1006148
Copyright_xml – notice: COPYRIGHT 2017 Public Library of Science
– notice: 2017 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Doria-Rose NA, Altae-Tran HR, Roark RS, Schmidt SD, Sutton MS, Louder MK, et al. (2017) Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting. PLoS Pathog 13(1): e1006148. doi:10.1371/journal.ppat.1006148
– notice: 2017 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Doria-Rose NA, Altae-Tran HR, Roark RS, Schmidt SD, Sutton MS, Louder MK, et al. (2017) Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting. PLoS Pathog 13(1): e1006148. doi:10.1371/journal.ppat.1006148
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Conceived and designed the experiments: ISG NADR HRAT.Performed the experiments: NADR HRAT RSR SDS MSS RTB GYC MKL KM SO FW ISG.Analyzed the data: NADR HRAT RSR SDS MSS RTB GYC MKL KM SO FW PDK JRM ISG.Contributed reagents/materials/analysis tools: VC RK MKL SSAK MC BFH MAM DCM LM JO.Wrote the paper: NADR HRAT JRM LM JMB ISG.
The authors have declared that no competing interests exist.
ORCID 0000-0002-4986-2133
0000-0003-1779-5885
0000-0002-6845-9905
0000-0002-1267-5596
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Snippet Computational neutralization fingerprinting, NFP, is an efficient and accurate method for predicting the epitope specificities of polyclonal antibody responses...
  Computational neutralization fingerprinting, NFP, is an efficient and accurate method for predicting the epitope specificities of polyclonal antibody...
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StartPage e1006148
SubjectTerms Acquired immune deficiency syndrome
AIDS
AIDS Vaccines - immunology
Algorithms
Analysis
Antibodies
Antibody Formation
Antibody Specificity
Antigenic determinants
Biology
Biology and Life Sciences
Cohort Studies
Colleges & universities
Computer Simulation
Epitope Mapping - methods
Epitopes - immunology
Experiments
Health aspects
HIV
HIV Antibodies - immunology
HIV Infections - immunology
HIV Infections - virology
HIV-1 - immunology
Human immunodeficiency virus
Humans
Immunology
Infections
Lentivirus
Medical research
Medicine and Health Sciences
Neutralization
Neutralization Tests
Physical Sciences
Physiological aspects
Polyclonal antibodies
Research and Analysis Methods
Retroviridae
Vaccines
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Title Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting
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Volume 13
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