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The Thai Phase III HIV Type 1 Vaccine trial (RV144) regimen induces antibodies that target conserved regions within the V2 loop of gp120.


ABSTRACT: The Thai Phase III clinical trial (RV144) showed modest efficacy in preventing HIV-1 acquisition. Plasma collected from HIV-1-uninfected trial participants completing all injections with ALVAC-HIV (vCP1521) prime and AIDSVAX B/E boost were tested for antibody responses against HIV-1 gp120 envelope (Env). Peptide microarray analysis from six HIV-1 subtypes and group M consensus showed that vaccination induced antibody responses to the second variable (V2) loop of gp120 of multiple subtypes. We further evaluated V2 responses by ELISA and surface plasmon resonance using cyclic (Cyc) and linear V2 loop peptides. Thirty-one of 32 vaccine recipients tested (97%) had antibody responses against Cyc V2 at 2 weeks postimmunization with a reciprocal geometric mean titer (GMT) of 1100 (range: 200-3200). The frequency of detecting plasma V2 antibodies declined to 19% at 28 weeks post-last injection (GMT: 110, range: 100-200). Antibody responses targeted the mid-region of the V2 loop that contains conserved epitopes and has the amino acid sequence KQKVHALFYKLDIVPI (HXB2 Numbering sequence 169-184). Valine at position 172 was critical for antibody binding. The frequency of V3 responses at 2 weeks postimmunization was modest (18/32, 56%) with a GMT of 185 (range: 100-800). In contrast, naturally infected HIV-1 individuals had a lower frequency of antibody responses to V2 (10/20, 50%; p=0.003) and a higher frequency of responses to V3 (19/20, 95%), with GMTs of 400 (range: 100-3200) and 3570 (range: 200-12,800), respectively. RV144 vaccination induced antibodies that targeted a region of the V2 loop that contains conserved epitopes. Early HIV-1 transmission events involve V2 loop interactions, raising the possibility that anti-V2 antibodies in RV144 may have contributed to viral inhibition.

SUBMITTER: Karasavvas N 

PROVIDER: S-EPMC3484815 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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The Thai Phase III HIV Type 1 Vaccine trial (RV144) regimen induces antibodies that target conserved regions within the V2 loop of gp120.

Karasavvas Nicos N   Billings Erik E   Rao Mangala M   Williams Constance C   Zolla-Pazner Susan S   Bailer Robert T RT   Koup Richard A RA   Madnote Sirinan S   Arworn Duangnapa D   Shen Xiaoying X   Tomaras Georgia D GD   Currier Jeffrey R JR   Jiang Mike M   Magaret Craig C   Andrews Charla C   Gottardo Raphael R   Gilbert Peter P   Cardozo Timothy J TJ   Rerks-Ngarm Supachai S   Nitayaphan Sorachai S   Pitisuttithum Punnee P   Kaewkungwal Jaranit J   Paris Robert R   Greene Kelli K   Gao Hongmei H   Gurunathan Sanjay S   Tartaglia Jim J   Sinangil Faruk F   Korber Bette T BT   Montefiori David C DC   Mascola John R JR   Robb Merlin L ML   Haynes Barton F BF   Ngauy Viseth V   Michael Nelson L NL   Kim Jerome H JH   de Souza Mark S MS  

AIDS research and human retroviruses 20121004 11


The Thai Phase III clinical trial (RV144) showed modest efficacy in preventing HIV-1 acquisition. Plasma collected from HIV-1-uninfected trial participants completing all injections with ALVAC-HIV (vCP1521) prime and AIDSVAX B/E boost were tested for antibody responses against HIV-1 gp120 envelope (Env). Peptide microarray analysis from six HIV-1 subtypes and group M consensus showed that vaccination induced antibody responses to the second variable (V2) loop of gp120 of multiple subtypes. We fu  ...[more]

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