Frequent Anti-V1V2 Responses Induced by HIV-DNA Followed by HIV-MVA with or without CN54rgp140/GLA-AF in Healthy African Volunteers.

Frank Msafiri,Arne Kroidl,Charlotta Nilsson,Mangala Rao,Yuka Nadai,Agricola Joachim,Gunnel Biberfeld,Muhammad Bakari,Eric Sandström,Merlin L Robb,Guido Ferrari,Kathrin Held,Christof Geldmacher,Raquel Matavele Chissumba,Edna Viegas,Sarah Joseph,Said Aboud,Sheena Mccormack,Wolfgang Stöhr,Eligius Lyamuya,Patricia Munseri ,Ilesh Jani,Britta Wahrén

doi:10.3390/microorganisms8111722

Abstract

Antibody responses that correlated with reduced risk of HIV acquisition in the RV144 efficacy trial were assessed in healthy African volunteers who had been primed three times with HIV-DNA (subtype A, B, C) and then randomized into two groups; group 1 was boosted twice with HIV-MVA (CRF01_AE) and group 2 with the same HIV-MVA coadministered with subtype C envelope (Env) protein (CN54rgp140/GLA-AF). The fine specificity of plasma Env-specific antibody responses was mapped after the final vaccination using linear peptide microarray technology. Binding IgG antibodies to the V1V2 loop in CRF01_AE and subtype C Env and Env-specific IgA antibodies were determined using enzyme-linked immunosorbent assay. Functional antibody-dependent cellular cytotoxicity (ADCC)-mediating antibody responses were measured using luciferase assay. Mapping of linear epitopes within HIV-1 Env demonstrated strong targeting of the V1V2, V3, and the immunodominant region in gp41 in both groups, with additional recognition of two epitopes located in the C2 and C4 regions in group 2. A high frequency of V1V2-specific binding IgG antibody responses was detected to CRF01_AE (77%) and subtype C antigens (65%). In conclusion, coadministration of CN54rgp140/GLA-AF with HIV-MVA did not increase the frequency, breadth, or magnitude of anti-V1V2 responses or ADCC-mediating antibodies induced by boosting with HIV-MVA alone.

Highlights

Ultimate control of the HIV pandemic depends on availability of a vaccine that can curtail new HIV infections [1,2,3,4]
Two additional immunodominant regions (IDR) were observed in samples from group 2: IDR2_C2 in the constant (C) region 2 and IDR4_C4 in C4, containing one of the amino acids that make up the CD4 binding site
We report induction of antibody responses that correlated with reduced risk of HIV acquisition in the RV144 efficacy trial [37,39]

Summary

Introduction

Ultimate control of the HIV pandemic depends on availability of a vaccine that can curtail new HIV infections [1,2,3,4]. In an ongoing HIV efficacy trial, an Adenovirus-26 vector prime and clade C gp140 boost regimen is being tested among women in sub-Saharan Africa [15], and among men who have sex with men and transgender people in the Americas and in Europe [16]. HIV-1 vaccine regimens consisting of recombinant DNA primes and vector-based boosts have been demonstrated to be safe and highly immunogenic [18,19,20,21,22]. The safety, immunogenicity, optimal dose, and route of delivery of a multigene, multiclade HIV-DNA priming vaccinations followed by boosting with heterologous HIV-1 modified vaccinia virus Ankara (MVA)-Chiang Mai double recombinant (CMDR) vaccine (HIV-MVA) have been evaluated in several phase I/II HIV vaccine trials [23,24,25,26,27,28]. Potent and durable immune responses were elicited after priming three times with HIV-1 DNA vaccine and boosting twice with HIV-MVA immunizations [29,30]

Methods

Results

Conclusion