ALVAC-HIV B/C candidate HIV vaccine efficacy dependent on neutralization profile of challenge virus and adjuvant dose and type

Abstract

The ALVAC-HIV clade B/AE and equivalent SIV-based/gp120 + Alum vaccines successfully decreased the risk of virus acquisition in humans and macaques. Here, we tested the efficacy of HIV clade B/C ALVAC/gp120 vaccine candidates + MF59 or different doses of Aluminum hydroxide (Alum) against SHIV-Cs of varying neutralization sensitivity in macaques. Low doses of Alum induced higher mucosal V2-specific IgA that increased the risk of Tier 2 SHIV-C acquisition. High Alum dosage, in contrast, elicited serum IgG to V2 that correlated with a decreased risk of Tier 1 SHIV-C acquisition. MF59 induced negligible mucosal antibodies to V2 and an inflammatory profile with blood C-reactive Protein (CRP) levels correlating with neutralizing antibody titers. MF59 decreased the risk of Tier 1 SHIV-C acquisition. The relationship between vaccine efficacy and the neutralization profile of the challenge virus appear to be linked to the different immunological spaces created by MF59 and Alum via CXCL10 and IL-1β, respectively.

Recognition Patterns of the C1/C2 Epitopes Involved in Fc-Mediated Response in HIV-1 Natural Infection and the RV114 Vaccine Trial

“…As we have previously published (43), adjuvant choice also makes a difference in the elicitation of ADCC-capable antibodies. Recently, Schifanella et al showed adjuvant choice and concentration had a strong influence on outcome for ALVAC-HIV B/E-induced protection in macaques (44). The adjuvant used for RV144 was an aluminum hydroxide gel, while HTVN 702 used MF59, an oil-in-water emulsion.…”

Adjuvanted HIV-1 vaccine promotes antibody-dependent phagocytic responses and protects against heterologous SHIV challenge

“…Animals were challenged simultaneously over two consecutive days or on a single day when fewer than 24 animals remained uninfected. The subtype C SHIV-1157ipd3N4 virus was selected as a stringent challenge strain for its tier 2 neutralization profile, heterologous sequence to the vaccine immunogens, and resistance to vaccine-mediated immunity [ 21 , 22 ]. The sequence distance between gp145 and the challenge strain is comparable to that between two randomly selected sequences within an HIV-1 subtype.…”

“…ALFA is believed to be an improvement to the highly successful but proprietary AS04 adjuvant, which contains free MPLA adsorbed to alum, and neither of these have been assessed for vaccination against HIV-1. Protection was determined by limiting-dose serial intrarectal challenge with the heterologous, tier 2, CCR5-tropic subtype C SHIV-1157ipd3N4 virus strain, considered to be a stringent model with limited vaccine efficacy achieved to date [20][21][22]. Adjuvanting with ALFA, but not alum, dramatically reduced the per-exposure infection risk, however, protection was limited to male animals.…”

Injection site vaccinology of a recombinant vaccinia-based vector reveals diverse innate immune signatures

“…CCL2 is also induced by MVA [ 154 ], can be important for avoiding immunopathology [ 51 ], and is induced by the licensed adjuvants, Alum and MF59 [ 205 ]. CXCL10 is also induced by MVA [ 206 ] and by the licensed adjuvant, MF59 [ 207 ]. Given the extensive clinical safety record of MVA vaccination [ 208 ] and the lack of overt injection site reactogenicity or fever observed in NHPs after SCV-ZIKA/CHIK vaccination [ 22 ], CCL2 and CXCL10 up-regulation at the injection site would thus not appear to be compelling biomarkers for adverse events after MVA or SCV vaccination.…”