Early Vaccine-Induced V1V2 Antibody Responses in Four Pox-Protein Public Private Partnership HIV Vaccine Trials

Background: RV144 demonstrated modest HIV preventive vaccine efficacy in Thailand. Amongst multiple identified correlates, IgG V1V2 antibodies were associated with 43% HIV risk reduction. The P5 aimed to further this by investigating subtype C vaccine regimens with different vectors (canarypox, DNA plasmid), adjuvants (alum, MF59, AS01.sub.B], or none), gp120 protein doses (40mcg, 200mcg, 600mcg), dosing strategies (prime-boost, co-administration) and administration methods (needle-syringe, Biojector). We compare IgG V1V2 responses across P5 trials with available data. Methods: In the HVTN100, HVTN107, HVTN108, and HVTN111 trials, serum specimens were obtained two weeks after the fourth vaccination. We measured the frequency and, amongst positive responders, the magnitude (MFI*: background-subtracted mean fluorescence intensity minus blank responses) of HIV-1-specific IgG (1:50 dilution) responses against V1V2 antigens for subtype C, gp70-TV1.GSKvacV1V2/293F (matched to subtype C protein vaccine), or subtype CRF01_AE, AE.A244 V1V2 Tags/293F (matched to subtype B/E protein vaccine), depending on protein administered. Responses were measured on Bio-Rad using a standardized custom Luminex HIV-1 binding antibody multiplex assay. Results: Amongst these subtype C regimens, the lowest response rate was induced by a regimen of two subtype C ALVAC primes followed by three boosts of subtype C ALVAC +200 mcg unadjuvanted gp120 (4/17 = 23.5%, CI 9.6%-47.3%); median magnitude 727.1MFI* (IQR 430.1 to 1152.1). The highest response rates were in co-administration groups of adjuvanted protein plus DNA or ALVAC at all timepoints). Rates, median magnitudes were 93.8%, 12124.8MFI* (DNA +40 mcg gp120 + [AS01.sub.B] at 3 timepoints); 91.4%, 21756.9MFI* (DNA + 200 mcg gp120 + [AS01.sub.B] at 3 timepoints); 89.1%, 7147.25MFI* (DNA + 200 mcg gp120 + MF59 by needle-syringe at 3 timepoints); 88.5%, 7745MFI* (DNA by Biojector + 200 mcg gp120 + MF59 by needle-syringe at 3 timepoints); 86.7%, 6205.1MFI* (subtype C ALVAC + 200 mcg gp120 + MF59 at 4 timepoints). For subtype C regimens, pooled response rates were higher for: (i) co-administration regimens versus regimens omitting protein in the first two doses (152/169 = 89.9% versus 233/374 = 62.3%, p < 0.00,001) and (ii) groups with DNA vaccines versus those with ALVAC (202/253 = 79.8% versus 187/299 = 62.5%, p < 0.00,001). Conclusions: Strategies which optimized IgG V1V2 responses in P5 subtype C vaccine trials included adjuvanted prot