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

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

doi:10.3390/microorganisms8111722

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

Microorganisms. 2020 Nov 4;8(11):1722. doi: 10.3390/microorganisms8111722.

Authors

Frank Msafiri^{1

2}, Agricola Joachim¹, Kathrin Held^{3

4}, Yuka Nadai^{3

4}, Raquel Matavele Chissumba⁵, Christof Geldmacher^{3

4}, Said Aboud¹, Wolfgang Stöhr⁶, Edna Viegas⁵, Arne Kroidl^{3

4}, Muhammad Bakari⁷, Patricia J Munseri⁷, Britta Wahren⁸, Eric Sandström⁹, Merlin L Robb¹⁰, Sheena McCormack⁶, Sarah Joseph¹¹, Ilesh Jani⁵, Guido Ferrari¹², Mangala Rao¹³, Gunnel Biberfeld¹⁴, Eligius Lyamuya¹, Charlotta Nilsson^{2

15}

Affiliations

¹ Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar es Salaam P.O. Box 65001, Tanzania.
² Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, 17177 Stockholm, Sweden.
³ Division of Infectious Diseases and Tropical Medicine, University Hospital, LMU Munich, 80802 Munich, Germany.
⁴ German Center for Infection Research (DZIF), partner site Munich, 80802 Munich, Germany.
⁵ Instituto Nacional de Saúde, Maputo 3943, Mozambique.
⁶ MRC Clinical Trials Unit at UCL, London WC1V 6LJ, UK.
⁷ Department of Internal Medicine, Muhimbili University of Health and Allied Sciences, Dar es Salaam P.O. Box 65001, Tanzania.
⁸ Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobel's Rd 16, 17177 Stockholm, Sweden.
⁹ Karolinska Institutet at Södersjukhuset, Södersjukhuset, 11883 Stockholm, Sweden.
¹⁰ The Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA.
¹¹ Imperial College London, London SW10 9NH, UK.
¹² Department of Surgery and Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
¹³ United States Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
¹⁴ Department of Global Public Health, Karolinska Institutet, 17177 Stockholm, Sweden.
¹⁵ Department of Microbiology, Public Health Agency of Sweden, 17182 Solna, Sweden.

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.

Keywords: African vaccinees; CN54rgp140 vaccine; HIV vaccine; HIV-DNA/MVA; V1V2 antibodies.

Abstract

Grants and funding