Epitopes described in "Vaccine induction of antibodies against a structurally heterogeneous site of immune pressure within HIV-1 envelope protein variable regions 1 and 2."

Article Authors:Hua-Xin Liao; Mattia Bonsignori; S Munir Alam; Jason S McLellan; Georgia D Tomaras; M Anthony Moody; Daniel M Kozink; Kwan-Ki Hwang; Xi Chen; Chun-Yen Tsao; Pinghuang Liu; Xiaozhi Lu; Robert J Parks; David C Montefiori; Guido Ferrari; Justin Pollara; Mangala Rao; Kristina K Peachman; Sampa Santra; Norman L Letvin; Nicos Karasavvas; Zhi-Yong Yang; Kaifan Dai; Marie Pancera; Jason Gorman; Kevin Wiehe; Nathan I Nicely; Supachai Rerks-Ngarm; Sorachai Nitayaphan; Jaranit Kaewkungwal; Punnee Pitisuttithum; James Tartaglia; Faruk Sinangil; Jerome H Kim; Nelson L Michael; Thomas B Kepler; Peter D Kwong; John R Mascola; Gary J Nabel; Abraham Pinter; Susan Zolla-Pazner; Barton F Haynes
Article Title:Vaccine induction of antibodies against a structurally heterogeneous site of immune pressure within HIV-1 envelope protein variable regions 1 and 2.
Reference Detail
Reference ID:1025510
Abstract:The RV144 HIV-1 trial of the canary pox vector (ALVAC-HIV) plus the gp120 AIDSVAX B/E vaccine demonstrated an estimated efficacy of 31%, which correlated directly with antibodies to HIV-1 envelope variable regions 1 and 2 (V1-V2). Genetic analysis of trial viruses revealed increased vaccine efficacy against viruses matching the vaccine strain at V2 residue 169. Here, we isolated four V2 monoclonal antibodies from RV144 vaccinees that recognize residue 169, neutralize laboratory-adapted HIV-1, and mediate killing of field-isolate HIV-1-infected CD4(+) T cells. Crystal structures of two of the V2 antibodies demonstrated that residue 169 can exist within divergent helical and loop conformations, which contrasted dramatically with the strand conformation previously observed with a broadly neutralizing antibody PG9. Thus, RV144 vaccine-induced immune pressure appears to target a region that may be both sequence variable and structurally polymorphic. Variation may signal sites of HIV-1 envelope vulnerability, providing vaccine designers with new options.
Affiliations:Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA. hliao@duke.edu.
Reference Type:Literature
PubMed ID:23313589
Journal Volume:38
Article Pages:176-86
Journal ISSN:1074-7613
Article Chemical List:AIDS Vaccines;AIDSVAX;Antibodies, Monoclonal;HIV Antibodies;HIV Envelope Protein gp120;Peptides
Article MeSH List:AIDS Vaccines(immunology); Amino Acid Sequence; Amino Acid Substitution(immunology); Antibodies, Monoclonal(immunology; metabolism); HIV Antibodies(chemistry; immunology; metabolism); HIV Envelope Protein gp120(chemistry; immunology; metabolism); Humans; Molecular Docking Simulation; Molecular Sequence Data; Peptides(chemistry; immunology; metabolism); Protein Binding(immunology); Protein Conformation
Curation Last Updated:2015-06-07 20:22:50