Comprehensive sieve analysis of breakthrough HIV-1 sequences in the RV144 vaccine efficacy trial.
Identifieur interne : 001710 ( PubMed/Corpus ); précédent : 001709; suivant : 001711Comprehensive sieve analysis of breakthrough HIV-1 sequences in the RV144 vaccine efficacy trial.
Auteurs : Paul T. Edlefsen ; Morgane Rolland ; Tomer Hertz ; Sodsai Tovanabutra ; Andrew J. Gartland ; Allan C. Decamp ; Craig A. Magaret ; Hasan Ahmed ; Raphael Gottardo ; Michal Juraska ; Connor Mccoy ; Brendan B. Larsen ; Eric Sanders-Buell ; Chris Carrico ; Sergey Menis ; Gustavo H. Kijak ; Meera Bose ; Miguel A. Arroyo ; Robert J. O'Connell ; Sorachai Nitayaphan ; Punnee Pitisuttithum ; Jaranit Kaewkungwal ; Supachai Rerks-Ngarm ; Merlin L. Robb ; Tatsiana Kirys ; Ivelin S. Georgiev ; Peter D. Kwong ; Konrad Scheffler ; Sergei L Kosakovsky Pond ; Jonathan M. Carlson ; Nelson L. Michael ; William R. Schief ; James I. Mullins ; Jerome H. Kim ; Peter B. GilbertSource :
- PLoS computational biology [ 1553-7358 ] ; 2015.
English descriptors
- KwdEn :
- AIDS Vaccines (genetics), AIDS Vaccines (immunology), Binding Sites (genetics), Genome, Viral (genetics), HIV Infections (immunology), HIV Infections (prevention & control), HIV Infections (virology), HIV-1 (genetics), HIV-1 (immunology), Human Immunodeficiency Virus Proteins (chemistry), Human Immunodeficiency Virus Proteins (genetics), Humans, Models, Molecular, Molecular Sequence Data, Sequence Alignment, Sequence Analysis, Protein.
- MESH :
- chemical , chemistry : Human Immunodeficiency Virus Proteins.
- chemical , genetics : AIDS Vaccines, Human Immunodeficiency Virus Proteins.
- chemical , immunology : AIDS Vaccines.
- genetics : Binding Sites, Genome, Viral, HIV-1.
- immunology : HIV Infections, HIV-1.
- prevention & control : HIV Infections.
- virology : HIV Infections.
- Humans, Models, Molecular, Molecular Sequence Data, Sequence Alignment, Sequence Analysis, Protein.
Abstract
The RV144 clinical trial showed the partial efficacy of a vaccine regimen with an estimated vaccine efficacy (VE) of 31% for protecting low-risk Thai volunteers against acquisition of HIV-1. The impact of vaccine-induced immune responses can be investigated through sieve analysis of HIV-1 breakthrough infections (infected vaccine and placebo recipients). A V1/V2-targeted comparison of the genomes of HIV-1 breakthrough viruses identified two V2 amino acid sites that differed between the vaccine and placebo groups. Here we extended the V1/V2 analysis to the entire HIV-1 genome using an array of methods based on individual sites, k-mers and genes/proteins. We identified 56 amino acid sites or "signatures" and 119 k-mers that differed between the vaccine and placebo groups. Of those, 19 sites and 38 k-mers were located in the regions comprising the RV144 vaccine (Env-gp120, Gag, and Pro). The nine signature sites in Env-gp120 were significantly enriched for known antibody-associated sites (p = 0.0021). In particular, site 317 in the third variable loop (V3) overlapped with a hotspot of antibody recognition, and sites 369 and 424 were linked to CD4 binding site neutralization. The identified signature sites significantly covaried with other sites across the genome (mean = 32.1) more than did non-signature sites (mean = 0.9) (p < 0.0001), suggesting functional and/or structural relevance of the signature sites. Since signature sites were not preferentially restricted to the vaccine immunogens and because most of the associations were insignificant following correction for multiple testing, we predict that few of the genetic differences are strongly linked to the RV144 vaccine-induced immune pressure. In addition to presenting results of the first complete-genome analysis of the breakthrough infections in the RV144 trial, this work describes a set of statistical methods and tools applicable to analysis of breakthrough infection genomes in general vaccine efficacy trials for diverse pathogens.
DOI: 10.1371/journal.pcbi.1003973
PubMed: 25646817
Links to Exploration step
pubmed:25646817Le document en format XML
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<author><name sortKey="Edlefsen, Paul T" sort="Edlefsen, Paul T" uniqKey="Edlefsen P" first="Paul T" last="Edlefsen">Paul T. Edlefsen</name>
<affiliation><nlm:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Rolland, Morgane" sort="Rolland, Morgane" uniqKey="Rolland M" first="Morgane" last="Rolland">Morgane Rolland</name>
<affiliation><nlm:affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Hertz, Tomer" sort="Hertz, Tomer" uniqKey="Hertz T" first="Tomer" last="Hertz">Tomer Hertz</name>
<affiliation><nlm:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America; The Shraga Segal Dept. of Microbiology, Immunology and Genetics, Faculty of Health Sciences, and The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva, Israel.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Tovanabutra, Sodsai" sort="Tovanabutra, Sodsai" uniqKey="Tovanabutra S" first="Sodsai" last="Tovanabutra">Sodsai Tovanabutra</name>
<affiliation><nlm:affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Gartland, Andrew J" sort="Gartland, Andrew J" uniqKey="Gartland A" first="Andrew J" last="Gartland">Andrew J. Gartland</name>
<affiliation><nlm:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Decamp, Allan C" sort="Decamp, Allan C" uniqKey="Decamp A" first="Allan C" last="Decamp">Allan C. Decamp</name>
<affiliation><nlm:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Magaret, Craig A" sort="Magaret, Craig A" uniqKey="Magaret C" first="Craig A" last="Magaret">Craig A. Magaret</name>
<affiliation><nlm:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Ahmed, Hasan" sort="Ahmed, Hasan" uniqKey="Ahmed H" first="Hasan" last="Ahmed">Hasan Ahmed</name>
<affiliation><nlm:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Gottardo, Raphael" sort="Gottardo, Raphael" uniqKey="Gottardo R" first="Raphael" last="Gottardo">Raphael Gottardo</name>
<affiliation><nlm:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Juraska, Michal" sort="Juraska, Michal" uniqKey="Juraska M" first="Michal" last="Juraska">Michal Juraska</name>
<affiliation><nlm:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Mccoy, Connor" sort="Mccoy, Connor" uniqKey="Mccoy C" first="Connor" last="Mccoy">Connor Mccoy</name>
<affiliation><nlm:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Larsen, Brendan B" sort="Larsen, Brendan B" uniqKey="Larsen B" first="Brendan B" last="Larsen">Brendan B. Larsen</name>
<affiliation><nlm:affiliation>Department of Microbiology, University of Washington, Seattle, Washington, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Sanders Buell, Eric" sort="Sanders Buell, Eric" uniqKey="Sanders Buell E" first="Eric" last="Sanders-Buell">Eric Sanders-Buell</name>
<affiliation><nlm:affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Carrico, Chris" sort="Carrico, Chris" uniqKey="Carrico C" first="Chris" last="Carrico">Chris Carrico</name>
<affiliation><nlm:affiliation>Department of Biochemistry, University of Washington, Seattle, Washington, United States of America; IAVI Neutralizing Antibody Center and Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, California, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Menis, Sergey" sort="Menis, Sergey" uniqKey="Menis S" first="Sergey" last="Menis">Sergey Menis</name>
<affiliation><nlm:affiliation>Department of Biochemistry, University of Washington, Seattle, Washington, United States of America; IAVI Neutralizing Antibody Center and Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, California, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Kijak, Gustavo H" sort="Kijak, Gustavo H" uniqKey="Kijak G" first="Gustavo H" last="Kijak">Gustavo H. Kijak</name>
<affiliation><nlm:affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Bose, Meera" sort="Bose, Meera" uniqKey="Bose M" first="Meera" last="Bose">Meera Bose</name>
<affiliation><nlm:affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Arroyo, Miguel A" sort="Arroyo, Miguel A" uniqKey="Arroyo M" first="Miguel A" last="Arroyo">Miguel A. Arroyo</name>
<affiliation><nlm:affiliation>Royal Thai Army Component, AFRIMS, Bangkok, Thailand.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="O Connell, Robert J" sort="O Connell, Robert J" uniqKey="O Connell R" first="Robert J" last="O'Connell">Robert J. O'Connell</name>
<affiliation><nlm:affiliation>US Army Component, AFRIMS, Bangkok, Thailand.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Nitayaphan, Sorachai" sort="Nitayaphan, Sorachai" uniqKey="Nitayaphan S" first="Sorachai" last="Nitayaphan">Sorachai Nitayaphan</name>
<affiliation><nlm:affiliation>Royal Thai Army Component, AFRIMS, Bangkok, Thailand.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Pitisuttithum, Punnee" sort="Pitisuttithum, Punnee" uniqKey="Pitisuttithum P" first="Punnee" last="Pitisuttithum">Punnee Pitisuttithum</name>
<affiliation><nlm:affiliation>Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Kaewkungwal, Jaranit" sort="Kaewkungwal, Jaranit" uniqKey="Kaewkungwal J" first="Jaranit" last="Kaewkungwal">Jaranit Kaewkungwal</name>
<affiliation><nlm:affiliation>Royal Thai Army Component, AFRIMS, Bangkok, Thailand.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Rerks Ngarm, Supachai" sort="Rerks Ngarm, Supachai" uniqKey="Rerks Ngarm S" first="Supachai" last="Rerks-Ngarm">Supachai Rerks-Ngarm</name>
<affiliation><nlm:affiliation>CDC Department, Thai Ministry of Public Health, Nonthaburi, Thailand.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Robb, Merlin L" sort="Robb, Merlin L" uniqKey="Robb M" first="Merlin L" last="Robb">Merlin L. Robb</name>
<affiliation><nlm:affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Kirys, Tatsiana" sort="Kirys, Tatsiana" uniqKey="Kirys T" first="Tatsiana" last="Kirys">Tatsiana Kirys</name>
<affiliation><nlm:affiliation>Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Georgiev, Ivelin S" sort="Georgiev, Ivelin S" uniqKey="Georgiev I" first="Ivelin S" last="Georgiev">Ivelin S. Georgiev</name>
<affiliation><nlm:affiliation>Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Kwong, Peter D" sort="Kwong, Peter D" uniqKey="Kwong P" first="Peter D" last="Kwong">Peter D. Kwong</name>
<affiliation><nlm:affiliation>Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Scheffler, Konrad" sort="Scheffler, Konrad" uniqKey="Scheffler K" first="Konrad" last="Scheffler">Konrad Scheffler</name>
<affiliation><nlm:affiliation>Department of Medicine, University of California, San Diego, La Jolla, California, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Pond, Sergei L Kosakovsky" sort="Pond, Sergei L Kosakovsky" uniqKey="Pond S" first="Sergei L Kosakovsky" last="Pond">Sergei L Kosakovsky Pond</name>
<affiliation><nlm:affiliation>Department of Medicine, University of California, San Diego, La Jolla, California, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Carlson, Jonathan M" sort="Carlson, Jonathan M" uniqKey="Carlson J" first="Jonathan M" last="Carlson">Jonathan M. Carlson</name>
<affiliation><nlm:affiliation>eSience Research Group, Microsoft Research, Redmond, Washington, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Michael, Nelson L" sort="Michael, Nelson L" uniqKey="Michael N" first="Nelson L" last="Michael">Nelson L. Michael</name>
<affiliation><nlm:affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Schief, William R" sort="Schief, William R" uniqKey="Schief W" first="William R" last="Schief">William R. Schief</name>
<affiliation><nlm:affiliation>Department of Biochemistry, University of Washington, Seattle, Washington, United States of America; IAVI Neutralizing Antibody Center and Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, California, United States of America; Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Mullins, James I" sort="Mullins, James I" uniqKey="Mullins J" first="James I" last="Mullins">James I. Mullins</name>
<affiliation><nlm:affiliation>Department of Microbiology, University of Washington, Seattle, Washington, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Kim, Jerome H" sort="Kim, Jerome H" uniqKey="Kim J" first="Jerome H" last="Kim">Jerome H. Kim</name>
<affiliation><nlm:affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Gilbert, Peter B" sort="Gilbert, Peter B" uniqKey="Gilbert P" first="Peter B" last="Gilbert">Peter B. Gilbert</name>
<affiliation><nlm:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</nlm:affiliation>
</affiliation>
</author>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Comprehensive sieve analysis of breakthrough HIV-1 sequences in the RV144 vaccine efficacy trial.</title>
<author><name sortKey="Edlefsen, Paul T" sort="Edlefsen, Paul T" uniqKey="Edlefsen P" first="Paul T" last="Edlefsen">Paul T. Edlefsen</name>
<affiliation><nlm:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Rolland, Morgane" sort="Rolland, Morgane" uniqKey="Rolland M" first="Morgane" last="Rolland">Morgane Rolland</name>
<affiliation><nlm:affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Hertz, Tomer" sort="Hertz, Tomer" uniqKey="Hertz T" first="Tomer" last="Hertz">Tomer Hertz</name>
<affiliation><nlm:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America; The Shraga Segal Dept. of Microbiology, Immunology and Genetics, Faculty of Health Sciences, and The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva, Israel.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Tovanabutra, Sodsai" sort="Tovanabutra, Sodsai" uniqKey="Tovanabutra S" first="Sodsai" last="Tovanabutra">Sodsai Tovanabutra</name>
<affiliation><nlm:affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Gartland, Andrew J" sort="Gartland, Andrew J" uniqKey="Gartland A" first="Andrew J" last="Gartland">Andrew J. Gartland</name>
<affiliation><nlm:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Decamp, Allan C" sort="Decamp, Allan C" uniqKey="Decamp A" first="Allan C" last="Decamp">Allan C. Decamp</name>
<affiliation><nlm:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Magaret, Craig A" sort="Magaret, Craig A" uniqKey="Magaret C" first="Craig A" last="Magaret">Craig A. Magaret</name>
<affiliation><nlm:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Ahmed, Hasan" sort="Ahmed, Hasan" uniqKey="Ahmed H" first="Hasan" last="Ahmed">Hasan Ahmed</name>
<affiliation><nlm:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Gottardo, Raphael" sort="Gottardo, Raphael" uniqKey="Gottardo R" first="Raphael" last="Gottardo">Raphael Gottardo</name>
<affiliation><nlm:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Juraska, Michal" sort="Juraska, Michal" uniqKey="Juraska M" first="Michal" last="Juraska">Michal Juraska</name>
<affiliation><nlm:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Mccoy, Connor" sort="Mccoy, Connor" uniqKey="Mccoy C" first="Connor" last="Mccoy">Connor Mccoy</name>
<affiliation><nlm:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Larsen, Brendan B" sort="Larsen, Brendan B" uniqKey="Larsen B" first="Brendan B" last="Larsen">Brendan B. Larsen</name>
<affiliation><nlm:affiliation>Department of Microbiology, University of Washington, Seattle, Washington, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Sanders Buell, Eric" sort="Sanders Buell, Eric" uniqKey="Sanders Buell E" first="Eric" last="Sanders-Buell">Eric Sanders-Buell</name>
<affiliation><nlm:affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Carrico, Chris" sort="Carrico, Chris" uniqKey="Carrico C" first="Chris" last="Carrico">Chris Carrico</name>
<affiliation><nlm:affiliation>Department of Biochemistry, University of Washington, Seattle, Washington, United States of America; IAVI Neutralizing Antibody Center and Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, California, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Menis, Sergey" sort="Menis, Sergey" uniqKey="Menis S" first="Sergey" last="Menis">Sergey Menis</name>
<affiliation><nlm:affiliation>Department of Biochemistry, University of Washington, Seattle, Washington, United States of America; IAVI Neutralizing Antibody Center and Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, California, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Kijak, Gustavo H" sort="Kijak, Gustavo H" uniqKey="Kijak G" first="Gustavo H" last="Kijak">Gustavo H. Kijak</name>
<affiliation><nlm:affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Bose, Meera" sort="Bose, Meera" uniqKey="Bose M" first="Meera" last="Bose">Meera Bose</name>
<affiliation><nlm:affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Arroyo, Miguel A" sort="Arroyo, Miguel A" uniqKey="Arroyo M" first="Miguel A" last="Arroyo">Miguel A. Arroyo</name>
<affiliation><nlm:affiliation>Royal Thai Army Component, AFRIMS, Bangkok, Thailand.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="O Connell, Robert J" sort="O Connell, Robert J" uniqKey="O Connell R" first="Robert J" last="O'Connell">Robert J. O'Connell</name>
<affiliation><nlm:affiliation>US Army Component, AFRIMS, Bangkok, Thailand.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Nitayaphan, Sorachai" sort="Nitayaphan, Sorachai" uniqKey="Nitayaphan S" first="Sorachai" last="Nitayaphan">Sorachai Nitayaphan</name>
<affiliation><nlm:affiliation>Royal Thai Army Component, AFRIMS, Bangkok, Thailand.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Pitisuttithum, Punnee" sort="Pitisuttithum, Punnee" uniqKey="Pitisuttithum P" first="Punnee" last="Pitisuttithum">Punnee Pitisuttithum</name>
<affiliation><nlm:affiliation>Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Kaewkungwal, Jaranit" sort="Kaewkungwal, Jaranit" uniqKey="Kaewkungwal J" first="Jaranit" last="Kaewkungwal">Jaranit Kaewkungwal</name>
<affiliation><nlm:affiliation>Royal Thai Army Component, AFRIMS, Bangkok, Thailand.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Rerks Ngarm, Supachai" sort="Rerks Ngarm, Supachai" uniqKey="Rerks Ngarm S" first="Supachai" last="Rerks-Ngarm">Supachai Rerks-Ngarm</name>
<affiliation><nlm:affiliation>CDC Department, Thai Ministry of Public Health, Nonthaburi, Thailand.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Robb, Merlin L" sort="Robb, Merlin L" uniqKey="Robb M" first="Merlin L" last="Robb">Merlin L. Robb</name>
<affiliation><nlm:affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Kirys, Tatsiana" sort="Kirys, Tatsiana" uniqKey="Kirys T" first="Tatsiana" last="Kirys">Tatsiana Kirys</name>
<affiliation><nlm:affiliation>Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Georgiev, Ivelin S" sort="Georgiev, Ivelin S" uniqKey="Georgiev I" first="Ivelin S" last="Georgiev">Ivelin S. Georgiev</name>
<affiliation><nlm:affiliation>Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Kwong, Peter D" sort="Kwong, Peter D" uniqKey="Kwong P" first="Peter D" last="Kwong">Peter D. Kwong</name>
<affiliation><nlm:affiliation>Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Scheffler, Konrad" sort="Scheffler, Konrad" uniqKey="Scheffler K" first="Konrad" last="Scheffler">Konrad Scheffler</name>
<affiliation><nlm:affiliation>Department of Medicine, University of California, San Diego, La Jolla, California, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Pond, Sergei L Kosakovsky" sort="Pond, Sergei L Kosakovsky" uniqKey="Pond S" first="Sergei L Kosakovsky" last="Pond">Sergei L Kosakovsky Pond</name>
<affiliation><nlm:affiliation>Department of Medicine, University of California, San Diego, La Jolla, California, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Carlson, Jonathan M" sort="Carlson, Jonathan M" uniqKey="Carlson J" first="Jonathan M" last="Carlson">Jonathan M. Carlson</name>
<affiliation><nlm:affiliation>eSience Research Group, Microsoft Research, Redmond, Washington, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Michael, Nelson L" sort="Michael, Nelson L" uniqKey="Michael N" first="Nelson L" last="Michael">Nelson L. Michael</name>
<affiliation><nlm:affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Schief, William R" sort="Schief, William R" uniqKey="Schief W" first="William R" last="Schief">William R. Schief</name>
<affiliation><nlm:affiliation>Department of Biochemistry, University of Washington, Seattle, Washington, United States of America; IAVI Neutralizing Antibody Center and Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, California, United States of America; Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Mullins, James I" sort="Mullins, James I" uniqKey="Mullins J" first="James I" last="Mullins">James I. Mullins</name>
<affiliation><nlm:affiliation>Department of Microbiology, University of Washington, Seattle, Washington, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Kim, Jerome H" sort="Kim, Jerome H" uniqKey="Kim J" first="Jerome H" last="Kim">Jerome H. Kim</name>
<affiliation><nlm:affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Gilbert, Peter B" sort="Gilbert, Peter B" uniqKey="Gilbert P" first="Peter B" last="Gilbert">Peter B. Gilbert</name>
<affiliation><nlm:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</nlm:affiliation>
</affiliation>
</author>
</analytic>
<series><title level="j">PLoS computational biology</title>
<idno type="eISSN">1553-7358</idno>
<imprint><date when="2015" type="published">2015</date>
</imprint>
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<term>AIDS Vaccines (immunology)</term>
<term>Binding Sites (genetics)</term>
<term>Genome, Viral (genetics)</term>
<term>HIV Infections (immunology)</term>
<term>HIV Infections (prevention & control)</term>
<term>HIV Infections (virology)</term>
<term>HIV-1 (genetics)</term>
<term>HIV-1 (immunology)</term>
<term>Human Immunodeficiency Virus Proteins (chemistry)</term>
<term>Human Immunodeficiency Virus Proteins (genetics)</term>
<term>Humans</term>
<term>Models, Molecular</term>
<term>Molecular Sequence Data</term>
<term>Sequence Alignment</term>
<term>Sequence Analysis, Protein</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Human Immunodeficiency Virus Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>AIDS Vaccines</term>
<term>Human Immunodeficiency Virus Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>AIDS Vaccines</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Binding Sites</term>
<term>Genome, Viral</term>
<term>HIV-1</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>HIV Infections</term>
<term>HIV-1</term>
</keywords>
<keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>HIV Infections</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>HIV Infections</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Humans</term>
<term>Models, Molecular</term>
<term>Molecular Sequence Data</term>
<term>Sequence Alignment</term>
<term>Sequence Analysis, Protein</term>
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<front><div type="abstract" xml:lang="en">The RV144 clinical trial showed the partial efficacy of a vaccine regimen with an estimated vaccine efficacy (VE) of 31% for protecting low-risk Thai volunteers against acquisition of HIV-1. The impact of vaccine-induced immune responses can be investigated through sieve analysis of HIV-1 breakthrough infections (infected vaccine and placebo recipients). A V1/V2-targeted comparison of the genomes of HIV-1 breakthrough viruses identified two V2 amino acid sites that differed between the vaccine and placebo groups. Here we extended the V1/V2 analysis to the entire HIV-1 genome using an array of methods based on individual sites, k-mers and genes/proteins. We identified 56 amino acid sites or "signatures" and 119 k-mers that differed between the vaccine and placebo groups. Of those, 19 sites and 38 k-mers were located in the regions comprising the RV144 vaccine (Env-gp120, Gag, and Pro). The nine signature sites in Env-gp120 were significantly enriched for known antibody-associated sites (p = 0.0021). In particular, site 317 in the third variable loop (V3) overlapped with a hotspot of antibody recognition, and sites 369 and 424 were linked to CD4 binding site neutralization. The identified signature sites significantly covaried with other sites across the genome (mean = 32.1) more than did non-signature sites (mean = 0.9) (p < 0.0001), suggesting functional and/or structural relevance of the signature sites. Since signature sites were not preferentially restricted to the vaccine immunogens and because most of the associations were insignificant following correction for multiple testing, we predict that few of the genetic differences are strongly linked to the RV144 vaccine-induced immune pressure. In addition to presenting results of the first complete-genome analysis of the breakthrough infections in the RV144 trial, this work describes a set of statistical methods and tools applicable to analysis of breakthrough infection genomes in general vaccine efficacy trials for diverse pathogens. </div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">25646817</PMID>
<DateCompleted><Year>2015</Year>
<Month>09</Month>
<Day>22</Day>
</DateCompleted>
<DateRevised><Year>2018</Year>
<Month>11</Month>
<Day>13</Day>
</DateRevised>
<Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Electronic">1553-7358</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>11</Volume>
<Issue>2</Issue>
<PubDate><Year>2015</Year>
<Month>Feb</Month>
</PubDate>
</JournalIssue>
<Title>PLoS computational biology</Title>
<ISOAbbreviation>PLoS Comput. Biol.</ISOAbbreviation>
</Journal>
<ArticleTitle>Comprehensive sieve analysis of breakthrough HIV-1 sequences in the RV144 vaccine efficacy trial.</ArticleTitle>
<Pagination><MedlinePgn>e1003973</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1371/journal.pcbi.1003973</ELocationID>
<Abstract><AbstractText>The RV144 clinical trial showed the partial efficacy of a vaccine regimen with an estimated vaccine efficacy (VE) of 31% for protecting low-risk Thai volunteers against acquisition of HIV-1. The impact of vaccine-induced immune responses can be investigated through sieve analysis of HIV-1 breakthrough infections (infected vaccine and placebo recipients). A V1/V2-targeted comparison of the genomes of HIV-1 breakthrough viruses identified two V2 amino acid sites that differed between the vaccine and placebo groups. Here we extended the V1/V2 analysis to the entire HIV-1 genome using an array of methods based on individual sites, k-mers and genes/proteins. We identified 56 amino acid sites or "signatures" and 119 k-mers that differed between the vaccine and placebo groups. Of those, 19 sites and 38 k-mers were located in the regions comprising the RV144 vaccine (Env-gp120, Gag, and Pro). The nine signature sites in Env-gp120 were significantly enriched for known antibody-associated sites (p = 0.0021). In particular, site 317 in the third variable loop (V3) overlapped with a hotspot of antibody recognition, and sites 369 and 424 were linked to CD4 binding site neutralization. The identified signature sites significantly covaried with other sites across the genome (mean = 32.1) more than did non-signature sites (mean = 0.9) (p < 0.0001), suggesting functional and/or structural relevance of the signature sites. Since signature sites were not preferentially restricted to the vaccine immunogens and because most of the associations were insignificant following correction for multiple testing, we predict that few of the genetic differences are strongly linked to the RV144 vaccine-induced immune pressure. In addition to presenting results of the first complete-genome analysis of the breakthrough infections in the RV144 trial, this work describes a set of statistical methods and tools applicable to analysis of breakthrough infection genomes in general vaccine efficacy trials for diverse pathogens. </AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Edlefsen</LastName>
<ForeName>Paul T</ForeName>
<Initials>PT</Initials>
<AffiliationInfo><Affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Rolland</LastName>
<ForeName>Morgane</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hertz</LastName>
<ForeName>Tomer</ForeName>
<Initials>T</Initials>
<AffiliationInfo><Affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America; The Shraga Segal Dept. of Microbiology, Immunology and Genetics, Faculty of Health Sciences, and The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva, Israel.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Tovanabutra</LastName>
<ForeName>Sodsai</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Gartland</LastName>
<ForeName>Andrew J</ForeName>
<Initials>AJ</Initials>
<AffiliationInfo><Affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>deCamp</LastName>
<ForeName>Allan C</ForeName>
<Initials>AC</Initials>
<AffiliationInfo><Affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Magaret</LastName>
<ForeName>Craig A</ForeName>
<Initials>CA</Initials>
<AffiliationInfo><Affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ahmed</LastName>
<ForeName>Hasan</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Gottardo</LastName>
<ForeName>Raphael</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Juraska</LastName>
<ForeName>Michal</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>McCoy</LastName>
<ForeName>Connor</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Larsen</LastName>
<ForeName>Brendan B</ForeName>
<Initials>BB</Initials>
<AffiliationInfo><Affiliation>Department of Microbiology, University of Washington, Seattle, Washington, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Sanders-Buell</LastName>
<ForeName>Eric</ForeName>
<Initials>E</Initials>
<AffiliationInfo><Affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Carrico</LastName>
<ForeName>Chris</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Department of Biochemistry, University of Washington, Seattle, Washington, United States of America; IAVI Neutralizing Antibody Center and Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, California, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Menis</LastName>
<ForeName>Sergey</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Department of Biochemistry, University of Washington, Seattle, Washington, United States of America; IAVI Neutralizing Antibody Center and Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, California, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kijak</LastName>
<ForeName>Gustavo H</ForeName>
<Initials>GH</Initials>
<AffiliationInfo><Affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bose</LastName>
<ForeName>Meera</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><CollectiveName>RV144 Sequencing Team</CollectiveName>
</Author>
<Author ValidYN="Y"><LastName>Arroyo</LastName>
<ForeName>Miguel A</ForeName>
<Initials>MA</Initials>
<AffiliationInfo><Affiliation>Royal Thai Army Component, AFRIMS, Bangkok, Thailand.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>O'Connell</LastName>
<ForeName>Robert J</ForeName>
<Initials>RJ</Initials>
<AffiliationInfo><Affiliation>US Army Component, AFRIMS, Bangkok, Thailand.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Nitayaphan</LastName>
<ForeName>Sorachai</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Royal Thai Army Component, AFRIMS, Bangkok, Thailand.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Pitisuttithum</LastName>
<ForeName>Punnee</ForeName>
<Initials>P</Initials>
<AffiliationInfo><Affiliation>Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kaewkungwal</LastName>
<ForeName>Jaranit</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Royal Thai Army Component, AFRIMS, Bangkok, Thailand.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Rerks-Ngarm</LastName>
<ForeName>Supachai</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>CDC Department, Thai Ministry of Public Health, Nonthaburi, Thailand.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Robb</LastName>
<ForeName>Merlin L</ForeName>
<Initials>ML</Initials>
<AffiliationInfo><Affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kirys</LastName>
<ForeName>Tatsiana</ForeName>
<Initials>T</Initials>
<AffiliationInfo><Affiliation>Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Georgiev</LastName>
<ForeName>Ivelin S</ForeName>
<Initials>IS</Initials>
<AffiliationInfo><Affiliation>Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kwong</LastName>
<ForeName>Peter D</ForeName>
<Initials>PD</Initials>
<AffiliationInfo><Affiliation>Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Scheffler</LastName>
<ForeName>Konrad</ForeName>
<Initials>K</Initials>
<AffiliationInfo><Affiliation>Department of Medicine, University of California, San Diego, La Jolla, California, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Pond</LastName>
<ForeName>Sergei L Kosakovsky</ForeName>
<Initials>SL</Initials>
<AffiliationInfo><Affiliation>Department of Medicine, University of California, San Diego, La Jolla, California, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Carlson</LastName>
<ForeName>Jonathan M</ForeName>
<Initials>JM</Initials>
<AffiliationInfo><Affiliation>eSience Research Group, Microsoft Research, Redmond, Washington, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Michael</LastName>
<ForeName>Nelson L</ForeName>
<Initials>NL</Initials>
<AffiliationInfo><Affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Schief</LastName>
<ForeName>William R</ForeName>
<Initials>WR</Initials>
<AffiliationInfo><Affiliation>Department of Biochemistry, University of Washington, Seattle, Washington, United States of America; IAVI Neutralizing Antibody Center and Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, California, United States of America; Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Mullins</LastName>
<ForeName>James I</ForeName>
<Initials>JI</Initials>
<AffiliationInfo><Affiliation>Department of Microbiology, University of Washington, Seattle, Washington, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kim</LastName>
<ForeName>Jerome H</ForeName>
<Initials>JH</Initials>
<AffiliationInfo><Affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Gilbert</LastName>
<ForeName>Peter B</ForeName>
<Initials>PB</Initials>
<AffiliationInfo><Affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
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<Language>eng</Language>
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</DataBank>
</DataBankList>
<GrantList CompleteYN="Y"><Grant><GrantID>UM1 AI100663</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R01 GM093939</GrantID>
<Acronym>GM</Acronym>
<Agency>NIGMS NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R37 AI054165</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>Y1-AI-2642-12</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>UM1 AI068635</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>2R37AI05465-11</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
</GrantList>
<PublicationTypeList><PublicationType UI="D017428">Clinical Trial, Phase III</PublicationType>
<PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D016449">Randomized Controlled Trial</PublicationType>
<PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType>
<PublicationType UI="D013486">Research Support, U.S. Gov't, Non-P.H.S.</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2015</Year>
<Month>02</Month>
<Day>03</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>PLoS Comput Biol</MedlineTA>
<NlmUniqueID>101238922</NlmUniqueID>
<ISSNLinking>1553-734X</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D016915">AIDS Vaccines</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D054298">Human Immunodeficiency Virus Proteins</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<CommentsCorrectionsList><CommentsCorrections RefType="ErratumIn"><RefSource>PLoS Comput Biol. 2016 Jan;12(1):e1004733</RefSource>
<PMID Version="1">26812465</PMID>
</CommentsCorrections>
</CommentsCorrectionsList>
<MeshHeadingList><MeshHeading><DescriptorName UI="D016915" MajorTopicYN="N">AIDS Vaccines</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D001665" MajorTopicYN="N">Binding Sites</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D016679" MajorTopicYN="N">Genome, Viral</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015658" MajorTopicYN="N">HIV Infections</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
<QualifierName UI="Q000517" MajorTopicYN="N">prevention & control</QualifierName>
<QualifierName UI="Q000821" MajorTopicYN="Y">virology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015497" MajorTopicYN="N">HIV-1</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D054298" MajorTopicYN="N">Human Immunodeficiency Virus Proteins</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008958" MajorTopicYN="N">Models, Molecular</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008969" MajorTopicYN="N">Molecular Sequence Data</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D016415" MajorTopicYN="N">Sequence Alignment</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D020539" MajorTopicYN="N">Sequence Analysis, Protein</DescriptorName>
</MeshHeading>
</MeshHeadingList>
<InvestigatorList><Investigator ValidYN="Y"><LastName>Howell</LastName>
<ForeName>Shana</ForeName>
<Initials>S</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Bates</LastName>
<ForeName>Adam</ForeName>
<Initials>A</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Lazzaro</LastName>
<ForeName>Michelle</ForeName>
<Initials>M</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>O'Sullivan</LastName>
<ForeName>Annemarie</ForeName>
<Initials>A</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Lei</LastName>
<ForeName>Esther</ForeName>
<Initials>E</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Bradfield</LastName>
<ForeName>Andrea</ForeName>
<Initials>A</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Ibitamuno</LastName>
<ForeName>Grace</ForeName>
<Initials>G</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Assawadarachai</LastName>
<ForeName>Vatcharain</ForeName>
<Initials>V</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Chen</LastName>
<ForeName>Lennie</ForeName>
<Initials>L</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Konopa</LastName>
<ForeName>Philip</ForeName>
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