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Analysis of V2 antibody responses induced in vaccinees in the ALVAC/AIDSVAX HIV-1 vaccine efficacy trial.

Publication ,  Journal Article
Zolla-Pazner, S; deCamp, AC; Cardozo, T; Karasavvas, N; Gottardo, R; Williams, C; Morris, DE; Tomaras, G; Rao, M; Billings, E; Berman, P ...
Published in: PLoS One
2013

The RV144 clinical trial of a prime/boost immunizing regimen using recombinant canary pox (ALVAC-HIV) and two gp120 proteins (AIDSVAX B and E) was previously shown to have a 31.2% efficacy rate. Plasma specimens from vaccine and placebo recipients were used in an extensive set of assays to identify correlates of HIV-1 infection risk. Of six primary variables that were studied, only one displayed a significant inverse correlation with risk of infection: the antibody (Ab) response to a fusion protein containing the V1 and V2 regions of gp120 (gp70-V1V2). This finding prompted a thorough examination of the results generated with the complete panel of 13 assays measuring various V2 Abs in the stored plasma used in the initial pilot studies and those used in the subsequent case-control study. The studies revealed that the ALVAC-HIV/AIDSVAX vaccine induced V2-specific Abs that cross-react with multiple HIV-1 subgroups and recognize both conformational and linear epitopes. The conformational epitope was present on gp70-V1V2, while the predominant linear V2 epitope mapped to residues 165-178, immediately N-terminal to the putative α4β7 binding motif in the mid-loop region of V2. Odds ratios (ORs) were calculated to compare the risk of infection with data from 12 V2 assays, and in 11 of these, the ORs were ≤1, reaching statistical significance for two of the variables: Ab responses to gp70-V1V2 and to overlapping V2 linear peptides. It remains to be determined whether anti-V2 Ab responses were directly responsible for the reduced infection rate in RV144 and whether anti-V2 Abs will prove to be important with other candidate HIV vaccines that show efficacy, however, the results support continued dissection of Ab responses to the V2 region which may illuminate mechanisms of protection from HIV-1 infection and may facilitate the development of an effective HIV-1 vaccine.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2013

Volume

8

Issue

1

Start / End Page

e53629

Location

United States

Related Subject Headings

  • Protein Structure, Tertiary
  • Peptides, Cyclic
  • Peptide Fragments
  • Molecular Sequence Data
  • Models, Molecular
  • Immunization, Secondary
  • Humans
  • HIV-1
  • HIV Envelope Protein gp120
  • General Science & Technology
 

Citation

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Chicago
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Zolla-Pazner, S., deCamp, A. C., Cardozo, T., Karasavvas, N., Gottardo, R., Williams, C., … Kim, J. H. (2013). Analysis of V2 antibody responses induced in vaccinees in the ALVAC/AIDSVAX HIV-1 vaccine efficacy trial. PLoS One, 8(1), e53629. https://doi.org/10.1371/journal.pone.0053629
Zolla-Pazner, Susan, Allan C. deCamp, Timothy Cardozo, Nicos Karasavvas, Raphael Gottardo, Constance Williams, Daryl E. Morris, et al. “Analysis of V2 antibody responses induced in vaccinees in the ALVAC/AIDSVAX HIV-1 vaccine efficacy trial.PLoS One 8, no. 1 (2013): e53629. https://doi.org/10.1371/journal.pone.0053629.
Zolla-Pazner S, deCamp AC, Cardozo T, Karasavvas N, Gottardo R, Williams C, et al. Analysis of V2 antibody responses induced in vaccinees in the ALVAC/AIDSVAX HIV-1 vaccine efficacy trial. PLoS One. 2013;8(1):e53629.
Zolla-Pazner, Susan, et al. “Analysis of V2 antibody responses induced in vaccinees in the ALVAC/AIDSVAX HIV-1 vaccine efficacy trial.PLoS One, vol. 8, no. 1, 2013, p. e53629. Pubmed, doi:10.1371/journal.pone.0053629.
Zolla-Pazner S, deCamp AC, Cardozo T, Karasavvas N, Gottardo R, Williams C, Morris DE, Tomaras G, Rao M, Billings E, Berman P, Shen X, Andrews C, O’Connell RJ, Ngauy V, Nitayaphan S, de Souza M, Korber B, Koup R, Bailer RT, Mascola JR, Pinter A, Montefiori D, Haynes BF, Robb ML, Rerks-Ngarm S, Michael NL, Gilbert PB, Kim JH. Analysis of V2 antibody responses induced in vaccinees in the ALVAC/AIDSVAX HIV-1 vaccine efficacy trial. PLoS One. 2013;8(1):e53629.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2013

Volume

8

Issue

1

Start / End Page

e53629

Location

United States

Related Subject Headings

  • Protein Structure, Tertiary
  • Peptides, Cyclic
  • Peptide Fragments
  • Molecular Sequence Data
  • Models, Molecular
  • Immunization, Secondary
  • Humans
  • HIV-1
  • HIV Envelope Protein gp120
  • General Science & Technology