TY - JOUR
T1 - Analysis of V2 Antibody Responses Induced in Vaccinees in the ALVAC/AIDSVAX HIV-1 Vaccine Efficacy Trial
AU - Zolla-Pazner, Susan
AU - deCamp, Allan C.
AU - Cardozo, Timothy
AU - Karasavvas, Nicos
AU - Gottardo, Raphael
AU - Williams, Constance
AU - Morris, Daryl E.
AU - Tomaras, Georgia
AU - Rao, Mangala
AU - Billings, Erik
AU - Berman, Phillip
AU - Shen, Xiaoying
AU - Andrews, Charla
AU - O'Connell, Robert J.
AU - Ngauy, Viseth
AU - Nitayaphan, Sorachai
AU - de Souza, Mark
AU - Korber, Bette
AU - Koup, Richard
AU - Bailer, Robert T.
AU - Mascola, John R.
AU - Pinter, Abraham
AU - Montefiori, David
AU - Haynes, Barton F.
AU - Robb, Merlin L.
AU - Rerks-Ngarm, Supachai
AU - Michael, Nelson L.
AU - Gilbert, Peter B.
AU - Kim, Jerome H.
N1 - Funding Information:
The RV144 clinical vaccine trial was registered with ClinicalTrials.gov; it was assigned NCT00223080 as the registration number. Written informed consent and counseling was conducted as described previously , and the protocol was reviewed by the ethics committees of the Thai Ministry of Public Health, the Royal Thai Army, Mahidol University, and the Human Subjects Research Review Board of the U.S. Army Medical Research and Materiel Command. It was also independently reviewed and endorsed by the World Health Organization, the Joint United Nations Program on HIV/AIDS, and by the AIDS Vaccine Research Working Group of the National Institute of Allergy and Infectious Diseases at the US National Institutes of Health. The manufacturers were full trial collaborators and were a part of the Phase III trial steering committee.
PY - 2013/1/17
Y1 - 2013/1/17
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84872514448&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0053629
DO - 10.1371/journal.pone.0053629
M3 - Article
C2 - 23349725
AN - SCOPUS:84872514448
SN - 1932-6203
VL - 8
JO - PLoS ONE
JF - PLoS ONE
IS - 1
M1 - e53629
ER -