IgG Antibody Responses to Recombinant gp120 Proteins, gp70V1/V2 Scaffolds, and a CyclicV2 Peptide in Thai Phase I/II Vaccine Trials Using Different Vaccine Regimens

Abstract

RV144 correlates of risk analysis showed that IgG antibodies to gp70V1V2 scaffolds inversely correlated with risk of HIV acquisition. We investigated IgG antibody responses in RV135 and RV132, two ALVAC-HIV prime-boost vaccine trials conducted in Thailand prior to RV144. Both trials used ALVAC-HIV (vCP1521) at 0, 1, 3, and 6 months and HIV-1 gp120MNgD and gp120A244gD in alum (RV135) or gp120SF2 and gp120CM235 in MF59 (RV132) at 3 and 6 months. We assessed ELISA binding antibodies to the envelope proteins (Env) 92TH023, A244gD and MNgD, cyclicV2, and gp70V1V2 CaseA2 (subtype B) and 92TH023 (subtype CRF01_AE), and Env-specific IgG1 and IgG3. Antibody responses to gp120 A244gD, MNgD, and gp70V1V2 92TH023 scaffold were significantly higher in RV135 than in RV132. Antibodies to gp70V1V2 CaseA2 were detected only in RV135 vaccine recipients and IgG1 and IgG3 antibody responses to A244gD were significantly higher in RV135. IgG binding to gp70V1V2 CaseA2 and CRF01_AE scaffolds was higher with the AIDSVAX(®)B/E boost but both trials showed similar rates of antibody decline post-vaccination. MF59 did not result in higher IgG antibody responses compared to alum with the antigens tested. However, notable differences in the structure of the recombinant proteins and dosage used for immunizations may have contributed to the magnitude and specificity of IgG induced by the two trials.

FIG. 1.

Alignment and percent identity of V2 loops and percent identity of HIV-1 gp120 envelopes. (A) Shaded sequences match HxB2 and boxed residues differ from the HxB2 reference strain. Amino acid sequences of the V2 loop are numbered based on the HxB2 reference strain. (B) Percent identity of the V2 loops. (C) Percent identity of gp120 Envs. RV132: HIV-1 gp120 92TH023 (CRF01_AE in ALVAC-HIV), CM235 (CRF01_AE), and SF2 (subtype B). RV135: HIV-1 gp120 92TH023 (CRF01_AE in ALVAC-HIV), A244 (CRF01_AE), and MN (subtype B).

FIG. 2.

Binding antibody geometric mean titers (GMT) to HIV-1 CRF01_AE rgp120 A244gD (A), to 92TH023 (B), and to HIV-1 subtype B MNgD (C) in RV135 (ALVAC-HIV prime with AIDSVAXB/E boost) and RV132 (ALVAC-HIV prime with CRF01_AE CM235 and subtype B SF2 boost) vaccine recipients. Pre-Vac: pre-vaccination; V5: 2 weeks post-first protein boost; V7: 2 weeks post-second protein boost; V10: 6 months post-second protein boost. Corrected p-value based on the Mann–Whitney test adjusted for multiple corrections using the Benjamini–Hochberg method.

FIG. 3.

Binding antibody geometric mean titers (GMT) to HIV-1 cyclic V2 peptide (A), to HIV-1 gp70 V1V2 CaseA2 (B), and to CRF01_AE 92TH023 (C) in RV135 (ALVAC-HIV prime with AIDSVAXB/E boost) and RV132 (ALVAC-HIV prime with CRF01_AE CM235 and subtype B SF2 boost) vaccine recipients. V5: 2 weeks post-first protein boost; V7: 2 weeks post-second protein boost; V10: 6 months post-second protein boost. Corrected p-value based on the Mann–Whitney test adjusted for multiple corrections using the Benjamini–Hochberg method.

FIG. 4.

IgG1 and IgG3 binding antibody geometric mean titers (GMT) to gp120 A244gD and scaffolded gp70 V1V2 proteins in RV135 (ALVAC-HIV prime with AIDSVAXB/E boost) and RV132 (ALVAC-HIV prime with CRF01_AE CM235 and subtype B SF2 boost) vaccine recipients. A244: HIV-1 CRF01_AE gp120 in AIDSVAX BE (RV135); gp70B: scaffolded gp70 V1V2 CaseA2 (subtype B); gp70E: scaffolded gp70 V1V2 92TH023 (CRF01_AE). V7: 2 weeks post-second protein boost. Corrected p-value based on the Mann–Whitney test adjusted for multiple corrections using the Benjamini–Hochberg method to control the false discovery rate.