Publication:
Boosting of HIV envelope CD4 binding site antibodies with long variable heavy third complementarity determining region in the randomized double blind RV305 HIV-1 vaccine trial

Issued Date

2017-02-01

Resource Type

Article

ISSN

15537374
15537366

DOI

10.1371/journal.ppat.1006182

Other identifier(s)

2-s2.0-85014071491

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

PLoS Pathogens. Vol.13, No.2 (2017)

Suggested Citation

David Easterhoff, M. Anthony Moody, Daniela Fera, Hao Cheng, Margaret Ackerman, Kevin Wiehe, Kevin O. Saunders, Justin Pollara, Nathan Vandergrift, Rob Parks, Jerome Kim, Nelson L. Michael, Robert J. O’Connell, Jean Louis Excler, Merlin L. Robb, Sandhya Vasan, Supachai Rerks-Ngarm, Jaranit Kaewkungwal, Punnee Pitisuttithum, Sorachai Nitayaphan, Faruk Sinangil, James Tartaglia, Sanjay Phogat, Thomas B. Kepler, S. Munir Alam, Hua Xin Liao, Guido Ferrari, Michael S. Seaman, David C. Montefiori, Georgia D. Tomaras, Stephen C. Harrison, Barton F. Haynes Boosting of HIV envelope CD4 binding site antibodies with long variable heavy third complementarity determining region in the randomized double blind RV305 HIV-1 vaccine trial. PLoS Pathogens. Vol.13, No.2 (2017). doi:10.1371/journal.ppat.1006182 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/42006

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Title

Boosting of HIV envelope CD4 binding site antibodies with long variable heavy third complementarity determining region in the randomized double blind RV305 HIV-1 vaccine trial

Author(s)

David Easterhoff
 M. Anthony Moody
 Daniela Fera
 Hao Cheng
 Margaret Ackerman
 Kevin Wiehe
 Kevin O. Saunders
 Justin Pollara
 Nathan Vandergrift
 Rob Parks
 Jerome Kim
 Nelson L. Michael
 Robert J. O’Connell
 Jean Louis Excler
 Merlin L. Robb
 Sandhya Vasan
 Supachai Rerks-Ngarm
 Jaranit Kaewkungwal
 Punnee Pitisuttithum
 Sorachai Nitayaphan
 Faruk Sinangil
 James Tartaglia
 Sanjay Phogat
 Thomas B. Kepler
 S. Munir Alam
 Hua Xin Liao
 Guido Ferrari
 Michael S. Seaman
 David C. Montefiori
 Georgia D. Tomaras
 Stephen C. Harrison
 Barton F. Haynes

Other Contributor(s)

Duke University
 Children's Hospital Boston
 Dartmouth College
 Walter Reed Army Institute of Research
 Armed Forces Research Institute of Medical Sciences, Thailand
 HJF
 Thailand Ministry of Public Health
 Mahidol University
 GSID
 Sanofi Pasteur
 Boston University
 Harvard Medical School
 International Vaccine Institute, Seoul

Abstract

© 2017 Public Library of Science. All Rights Reserved. The canary pox vector and gp120 vaccine (ALVAC-HIV and AIDSVAX B/E gp120) in the RV144 HIV-1 vaccine trial conferred an estimated 31% vaccine efficacy. Although the vaccine Env AE.A244 gp120 is antigenic for the unmutated common ancestor of V1V2 broadly neutralizing antibody (bnAbs), no plasma bnAb activity was induced. The RV305 (NCT01435135) HIV-1 clinical trial was a placebo-controlled randomized double-blinded study that assessed the safety and efficacy of vaccine boosting on B cell repertoires. HIV-1-uninfected RV144 vaccine recipients were reimmunized 6–8 years later with AIDSVAX B/E gp120 alone, ALVAC-HIV alone, or a combination of ALVAC-HIV and AIDSVAX B/E gp120 in the RV305 trial. Env-specific post-RV144 and RV305 boost memory B cell VHmutation frequencies increased from 2.9% post-RV144 to 6.7% post-RV305. The vaccine was well tolerated with no adverse events reports. While post-boost plasma did not have bnAb activity, the vaccine boosts expanded a pool of envelope CD4 binding site (bs)-reactive memory B cells with long third heavy chain complementarity determining regions (HCDR3) whose germline precursors and affinity matured B cell clonal lineage members neutralized the HIV-1 CRF01 AE tier 2 (difficult to neutralize) primary isolate, CNE8. Electron microscopy of two of these antibodies bound with near-native gp140 trimers showed that they recognized an open conformation of the Env trimer. Although late boosting of RV144 vaccinees expanded a novel pool of neutralizing B cell clonal lineages, we hypothesize that boosts with stably closed trimers would be necessary to elicit antibodies with greater breadth of tier 2 HIV-1 strains. Trial Registration: ClinicalTrials.gov NCT01435135

Keyword(s)

Biochemistry, Genetics and Molecular Biology
 Immunology and Microbiology

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/42006

Collections

Scopus 2016-2017