Vaccine Induction of Antibodies against a Structurally Heterogeneous Site of Immune Pressure within HIV-1 Envelope Protein Variable Regions 1 and 2

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• 作者：Hua-Xin Liao¹ ; ¹⁵ ; ^{hliao@duke.edu} ; Mattia Bonsignori¹ ; ¹⁵ ; S. Munir Alam¹ ; ¹⁵ ; Jason S. McLellan² ; ¹⁵ ; Georgia D. Tomaras¹ ; M. Anthony Moody¹ ; Daniel M. Kozink¹ ; Kwan-Ki Hwang¹ ; Xi Chen¹ ; Chun-Yen Tsao¹ ; Pinghuang Liu¹ ; Xiaozhi Lu¹ ; Robert J. Parks¹ ; David C. Montefiori¹ ; Guido Ferrari¹ ; Justin Pollara¹ ; Mangala Rao³ ; Kristina K. Peachman³ ; Sampa Santra⁴ ; Norman L. Letvin⁴ ; Nicos Karasavvas⁵ ; Zhi-Yong Yang² ; Kaifan Dai² ; Marie Pancera² ; Jason Gorman² ; Kevin Wiehe¹ ; Nathan I. Nicely¹ ; Supachai Rerks-Ngarm⁶ ; Sorachai Nitayaphan⁵ ; Jaranit Kaewkungwal⁷ ; Punnee Pitisuttithum⁸ ; James Tartaglia⁹ ; Faruk Sinangil¹⁰ ; Jerome H. Kim³ ; Nelson L. Michael³ ; Thomas B. Kepler¹¹ ; Peter D. Kwong² ; John R. Mascola² ; Gary J. Nabel² ; Abraham Pinter¹² ; Susan Zolla-Pazner¹³ ; ¹⁴ ; Barton F. Haynes¹ ; ^{hayne002@mc.duke.edu}
• 刊名：Immunity
• 出版年：2013
• 出版时间：24 January, 2013
• 年：2013
• 卷：38
• 期：1
• 页码：176-186
• 全文大小：1477 K

文摘

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Summary

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 ¦Â 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.