Comprehensive sieve analysis of breakthrough HIV-1 sequences in the RV144 vaccine efficacy trial.
Identifieur interne : 001600 ( PubMed/Checkpoint ); précédent : 001599; suivant : 001601Comprehensive sieve analysis of breakthrough HIV-1 sequences in the RV144 vaccine efficacy trial.
Auteurs : Paul T. Edlefsen [États-Unis] ; Morgane Rolland [États-Unis] ; Tomer Hertz [Israël] ; Sodsai Tovanabutra [États-Unis] ; Andrew J. Gartland [États-Unis] ; Allan C. Decamp [États-Unis] ; Craig A. Magaret [États-Unis] ; Hasan Ahmed [États-Unis] ; Raphael Gottardo [États-Unis] ; Michal Juraska [États-Unis] ; Connor Mccoy [États-Unis] ; Brendan B. Larsen [États-Unis] ; Eric Sanders-Buell [États-Unis] ; Chris Carrico [États-Unis] ; Sergey Menis [États-Unis] ; Gustavo H. Kijak [États-Unis] ; Meera Bose [États-Unis] ; Miguel A. Arroyo [Thaïlande] ; Robert J. O'Connell [Thaïlande] ; Sorachai Nitayaphan [Thaïlande] ; Punnee Pitisuttithum [Thaïlande] ; Jaranit Kaewkungwal [Thaïlande] ; Supachai Rerks-Ngarm [Thaïlande] ; Merlin L. Robb [États-Unis] ; Tatsiana Kirys [États-Unis] ; Ivelin S. Georgiev [États-Unis] ; Peter D. Kwong [États-Unis] ; Konrad Scheffler [États-Unis] ; Sergei L Kosakovsky Pond [États-Unis] ; Jonathan M. Carlson [États-Unis] ; Nelson L. Michael [États-Unis] ; William R. Schief [États-Unis] ; James I. Mullins [États-Unis] ; Jerome H. Kim [États-Unis] ; Peter B. Gilbert [États-Unis]Source :
- PLoS computational biology [ 1553-7358 ] ; 2015.
Descripteurs français
- KwdFr :
- Alignement de séquences, Analyse de séquence de protéine, Données de séquences moléculaires, Génome viral (génétique), Humains, Infections à VIH (), Infections à VIH (immunologie), Infections à VIH (virologie), Modèles moléculaires, Protéines du virus de l'immunodéficience humaine (), Protéines du virus de l'immunodéficience humaine (génétique), Sites de fixation (génétique), VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (génétique), VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (immunologie), Vaccins contre le SIDA (génétique), Vaccins contre le SIDA (immunologie).
- MESH :
- génétique : Génome viral, Protéines du virus de l'immunodéficience humaine, Sites de fixation, VIH-1 (Virus de l'Immunodéficience Humaine de type 1), Vaccins contre le SIDA.
- immunologie : Infections à VIH, VIH-1 (Virus de l'Immunodéficience Humaine de type 1), Vaccins contre le SIDA.
- virologie : Infections à VIH.
- Alignement de séquences, Analyse de séquence de protéine, Données de séquences moléculaires, Humains, Infections à VIH, Modèles moléculaires, Protéines du virus de l'immunodéficience humaine.
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
Affiliations:
- Israël, Thaïlande, États-Unis
- Californie, Maryland, Massachusetts, Washington (État)
- Seattle
- Université de Washington
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pubmed:25646817Le document en format XML
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<author><name sortKey="Gottardo, Raphael" sort="Gottardo, Raphael" uniqKey="Gottardo R" first="Raphael" last="Gottardo">Raphael Gottardo</name>
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<country xml:lang="fr">États-Unis</country>
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<author><name sortKey="Bose, Meera" sort="Bose, Meera" uniqKey="Bose M" first="Meera" last="Bose">Meera Bose</name>
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<author><name sortKey="Arroyo, Miguel A" sort="Arroyo, Miguel A" uniqKey="Arroyo M" first="Miguel A" last="Arroyo">Miguel A. Arroyo</name>
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<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>
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<author><name sortKey="Nitayaphan, Sorachai" sort="Nitayaphan, Sorachai" uniqKey="Nitayaphan S" first="Sorachai" last="Nitayaphan">Sorachai Nitayaphan</name>
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<author><name sortKey="Pitisuttithum, Punnee" sort="Pitisuttithum, Punnee" uniqKey="Pitisuttithum P" first="Punnee" last="Pitisuttithum">Punnee Pitisuttithum</name>
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<author><name sortKey="Kaewkungwal, Jaranit" sort="Kaewkungwal, Jaranit" uniqKey="Kaewkungwal J" first="Jaranit" last="Kaewkungwal">Jaranit Kaewkungwal</name>
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<author><name sortKey="Rerks Ngarm, Supachai" sort="Rerks Ngarm, Supachai" uniqKey="Rerks Ngarm S" first="Supachai" last="Rerks-Ngarm">Supachai Rerks-Ngarm</name>
<affiliation wicri:level="1"><nlm:affiliation>CDC Department, Thai Ministry of Public Health, Nonthaburi, Thailand.</nlm:affiliation>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>CDC Department, Thai Ministry of Public Health, Nonthaburi</wicri:regionArea>
<wicri:noRegion>Nonthaburi</wicri:noRegion>
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<author><name sortKey="Robb, Merlin L" sort="Robb, Merlin L" uniqKey="Robb M" first="Merlin L" last="Robb">Merlin L. Robb</name>
<affiliation wicri:level="2"><nlm:affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>US Military HIV Research Program, Silver Spring, Maryland</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kirys, Tatsiana" sort="Kirys, Tatsiana" uniqKey="Kirys T" first="Tatsiana" last="Kirys">Tatsiana Kirys</name>
<affiliation wicri:level="2"><nlm:affiliation>Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Vaccine Research Center, NIAID, NIH, Bethesda, Maryland</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</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 wicri:level="2"><nlm:affiliation>Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Vaccine Research Center, NIAID, NIH, Bethesda, Maryland</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</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 wicri:level="2"><nlm:affiliation>Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Vaccine Research Center, NIAID, NIH, Bethesda, Maryland</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Scheffler, Konrad" sort="Scheffler, Konrad" uniqKey="Scheffler K" first="Konrad" last="Scheffler">Konrad Scheffler</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Medicine, University of California, San Diego, La Jolla, California, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medicine, University of California, San Diego, La Jolla, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</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 wicri:level="2"><nlm:affiliation>Department of Medicine, University of California, San Diego, La Jolla, California, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medicine, University of California, San Diego, La Jolla, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</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 wicri:level="2"><nlm:affiliation>eSience Research Group, Microsoft Research, Redmond, Washington, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>eSience Research Group, Microsoft Research, Redmond, Washington</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
</placeName>
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<author><name sortKey="Michael, Nelson L" sort="Michael, Nelson L" uniqKey="Michael N" first="Nelson L" last="Michael">Nelson L. Michael</name>
<affiliation wicri:level="2"><nlm:affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>US Military HIV Research Program, Silver Spring, Maryland</wicri:regionArea>
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<author><name sortKey="Schief, William R" sort="Schief, William R" uniqKey="Schief W" first="William R" last="Schief">William R. Schief</name>
<affiliation wicri:level="4"><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>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>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</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
<settlement type="city">Seattle</settlement>
</placeName>
<orgName type="university">Université de Washington</orgName>
</affiliation>
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<author><name sortKey="Mullins, James I" sort="Mullins, James I" uniqKey="Mullins J" first="James I" last="Mullins">James I. Mullins</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology, University of Washington, Seattle, Washington, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
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</placeName>
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</author>
<author><name sortKey="Kim, Jerome H" sort="Kim, Jerome H" uniqKey="Kim J" first="Jerome H" last="Kim">Jerome H. Kim</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>US Military HIV Research Program, Silver Spring, Maryland</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</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 wicri:level="2"><nlm:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
</placeName>
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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 wicri:level="2"><nlm:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
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</affiliation>
</author>
<author><name sortKey="Rolland, Morgane" sort="Rolland, Morgane" uniqKey="Rolland M" first="Morgane" last="Rolland">Morgane Rolland</name>
<affiliation wicri:level="2"><nlm:affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>US Military HIV Research Program, Silver Spring, Maryland</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hertz, Tomer" sort="Hertz, Tomer" uniqKey="Hertz T" first="Tomer" last="Hertz">Tomer Hertz</name>
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<country xml:lang="fr">Israël</country>
<wicri:regionArea>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</wicri:regionArea>
<wicri:noRegion>Beer-Sheva</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Tovanabutra, Sodsai" sort="Tovanabutra, Sodsai" uniqKey="Tovanabutra S" first="Sodsai" last="Tovanabutra">Sodsai Tovanabutra</name>
<affiliation wicri:level="2"><nlm:affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>US Military HIV Research Program, Silver Spring, Maryland</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</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 wicri:level="2"><nlm:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
</placeName>
</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 wicri:level="2"><nlm:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
</placeName>
</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 wicri:level="2"><nlm:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ahmed, Hasan" sort="Ahmed, Hasan" uniqKey="Ahmed H" first="Hasan" last="Ahmed">Hasan Ahmed</name>
<affiliation wicri:level="2"><nlm:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gottardo, Raphael" sort="Gottardo, Raphael" uniqKey="Gottardo R" first="Raphael" last="Gottardo">Raphael Gottardo</name>
<affiliation wicri:level="2"><nlm:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Juraska, Michal" sort="Juraska, Michal" uniqKey="Juraska M" first="Michal" last="Juraska">Michal Juraska</name>
<affiliation wicri:level="2"><nlm:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mccoy, Connor" sort="Mccoy, Connor" uniqKey="Mccoy C" first="Connor" last="Mccoy">Connor Mccoy</name>
<affiliation wicri:level="2"><nlm:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
</placeName>
</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 wicri:level="4"><nlm:affiliation>Department of Microbiology, University of Washington, Seattle, Washington, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology, University of Washington, Seattle, Washington</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
<settlement type="city">Seattle</settlement>
</placeName>
<orgName type="university">Université de Washington</orgName>
</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 wicri:level="2"><nlm:affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>US Military HIV Research Program, Silver Spring, Maryland</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Carrico, Chris" sort="Carrico, Chris" uniqKey="Carrico C" first="Chris" last="Carrico">Chris Carrico</name>
<affiliation wicri:level="4"><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>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>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</wicri:regionArea>
<placeName><region type="state">Californie</region>
<settlement type="city">Seattle</settlement>
</placeName>
<orgName type="university">Université de Washington</orgName>
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</author>
<author><name sortKey="Menis, Sergey" sort="Menis, Sergey" uniqKey="Menis S" first="Sergey" last="Menis">Sergey Menis</name>
<affiliation wicri:level="4"><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>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>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</wicri:regionArea>
<placeName><region type="state">Californie</region>
<settlement type="city">Seattle</settlement>
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<orgName type="university">Université de Washington</orgName>
</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 wicri:level="2"><nlm:affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>US Military HIV Research Program, Silver Spring, Maryland</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bose, Meera" sort="Bose, Meera" uniqKey="Bose M" first="Meera" last="Bose">Meera Bose</name>
<affiliation wicri:level="2"><nlm:affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>US Military HIV Research Program, Silver Spring, Maryland</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Arroyo, Miguel A" sort="Arroyo, Miguel A" uniqKey="Arroyo M" first="Miguel A" last="Arroyo">Miguel A. Arroyo</name>
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<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Royal Thai Army Component, AFRIMS, Bangkok</wicri:regionArea>
<wicri:noRegion>Bangkok</wicri:noRegion>
</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 wicri:level="1"><nlm:affiliation>US Army Component, AFRIMS, Bangkok, Thailand.</nlm:affiliation>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>US Army Component, AFRIMS, Bangkok</wicri:regionArea>
<wicri:noRegion>Bangkok</wicri:noRegion>
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</author>
<author><name sortKey="Nitayaphan, Sorachai" sort="Nitayaphan, Sorachai" uniqKey="Nitayaphan S" first="Sorachai" last="Nitayaphan">Sorachai Nitayaphan</name>
<affiliation wicri:level="1"><nlm:affiliation>Royal Thai Army Component, AFRIMS, Bangkok, Thailand.</nlm:affiliation>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Royal Thai Army Component, AFRIMS, Bangkok</wicri:regionArea>
<wicri:noRegion>Bangkok</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Pitisuttithum, Punnee" sort="Pitisuttithum, Punnee" uniqKey="Pitisuttithum P" first="Punnee" last="Pitisuttithum">Punnee Pitisuttithum</name>
<affiliation wicri:level="1"><nlm:affiliation>Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.</nlm:affiliation>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Faculty of Tropical Medicine, Mahidol University, Bangkok</wicri:regionArea>
<wicri:noRegion>Bangkok</wicri:noRegion>
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</author>
<author><name sortKey="Kaewkungwal, Jaranit" sort="Kaewkungwal, Jaranit" uniqKey="Kaewkungwal J" first="Jaranit" last="Kaewkungwal">Jaranit Kaewkungwal</name>
<affiliation wicri:level="1"><nlm:affiliation>Royal Thai Army Component, AFRIMS, Bangkok, Thailand.</nlm:affiliation>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Royal Thai Army Component, AFRIMS, Bangkok</wicri:regionArea>
<wicri:noRegion>Bangkok</wicri:noRegion>
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</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 wicri:level="1"><nlm:affiliation>CDC Department, Thai Ministry of Public Health, Nonthaburi, Thailand.</nlm:affiliation>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>CDC Department, Thai Ministry of Public Health, Nonthaburi</wicri:regionArea>
<wicri:noRegion>Nonthaburi</wicri:noRegion>
</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 wicri:level="2"><nlm:affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>US Military HIV Research Program, Silver Spring, Maryland</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kirys, Tatsiana" sort="Kirys, Tatsiana" uniqKey="Kirys T" first="Tatsiana" last="Kirys">Tatsiana Kirys</name>
<affiliation wicri:level="2"><nlm:affiliation>Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Vaccine Research Center, NIAID, NIH, Bethesda, Maryland</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</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 wicri:level="2"><nlm:affiliation>Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Vaccine Research Center, NIAID, NIH, Bethesda, Maryland</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</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 wicri:level="2"><nlm:affiliation>Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Vaccine Research Center, NIAID, NIH, Bethesda, Maryland</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Scheffler, Konrad" sort="Scheffler, Konrad" uniqKey="Scheffler K" first="Konrad" last="Scheffler">Konrad Scheffler</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Medicine, University of California, San Diego, La Jolla, California, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medicine, University of California, San Diego, La Jolla, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</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 wicri:level="2"><nlm:affiliation>Department of Medicine, University of California, San Diego, La Jolla, California, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medicine, University of California, San Diego, La Jolla, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</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 wicri:level="2"><nlm:affiliation>eSience Research Group, Microsoft Research, Redmond, Washington, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>eSience Research Group, Microsoft Research, Redmond, Washington</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
</placeName>
</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 wicri:level="2"><nlm:affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>US Military HIV Research Program, Silver Spring, Maryland</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</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 wicri:level="4"><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>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>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</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
<settlement type="city">Seattle</settlement>
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<orgName type="university">Université de Washington</orgName>
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</author>
<author><name sortKey="Mullins, James I" sort="Mullins, James I" uniqKey="Mullins J" first="James I" last="Mullins">James I. Mullins</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology, University of Washington, Seattle, Washington, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology, University of Washington, Seattle, Washington</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
<settlement type="city">Seattle</settlement>
</placeName>
<orgName type="university">Université de Washington</orgName>
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</author>
<author><name sortKey="Kim, Jerome H" sort="Kim, Jerome H" uniqKey="Kim J" first="Jerome H" last="Kim">Jerome H. Kim</name>
<affiliation wicri:level="2"><nlm:affiliation>US Military HIV Research Program, Silver Spring, Maryland, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>US Military HIV Research Program, Silver Spring, Maryland</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</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 wicri:level="2"><nlm:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
</placeName>
</affiliation>
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</analytic>
<series><title level="j">PLoS computational biology</title>
<idno type="eISSN">1553-7358</idno>
<imprint><date when="2015" type="published">2015</date>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>AIDS Vaccines (genetics)</term>
<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="KwdFr" xml:lang="fr"><term>Alignement de séquences</term>
<term>Analyse de séquence de protéine</term>
<term>Données de séquences moléculaires</term>
<term>Génome viral (génétique)</term>
<term>Humains</term>
<term>Infections à VIH ()</term>
<term>Infections à VIH (immunologie)</term>
<term>Infections à VIH (virologie)</term>
<term>Modèles moléculaires</term>
<term>Protéines du virus de l'immunodéficience humaine ()</term>
<term>Protéines du virus de l'immunodéficience humaine (génétique)</term>
<term>Sites de fixation (génétique)</term>
<term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (génétique)</term>
<term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (immunologie)</term>
<term>Vaccins contre le SIDA (génétique)</term>
<term>Vaccins contre le SIDA (immunologie)</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="génétique" xml:lang="fr"><term>Génome viral</term>
<term>Protéines du virus de l'immunodéficience humaine</term>
<term>Sites de fixation</term>
<term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1)</term>
<term>Vaccins contre le SIDA</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Infections à VIH</term>
<term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1)</term>
<term>Vaccins contre le SIDA</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="virologie" xml:lang="fr"><term>Infections à VIH</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>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Alignement de séquences</term>
<term>Analyse de séquence de protéine</term>
<term>Données de séquences moléculaires</term>
<term>Humains</term>
<term>Infections à VIH</term>
<term>Modèles moléculaires</term>
<term>Protéines du virus de l'immunodéficience humaine</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>
</AuthorList>
<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>
<Initials>P</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Nariya</LastName>
<ForeName>Snehal</ForeName>
<Initials>S</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Stoddard</LastName>
<ForeName>Julia N</ForeName>
<Initials>JN</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Wong</LastName>
<ForeName>Kim</ForeName>
<Initials>K</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Zhao</LastName>
<ForeName>Hong</ForeName>
<Initials>H</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Deng</LastName>
<ForeName>Wenjie</ForeName>
<Initials>W</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Maust</LastName>
<ForeName>Brandon S</ForeName>
<Initials>BS</Initials>
</Investigator>
</InvestigatorList>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2014</Year>
<Month>07</Month>
<Day>24</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2014</Year>
<Month>10</Month>
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