Modifications to the HIV-1 SAAVI MVA-C vaccine improve in vitro expression and in vivo immunogenicity

Nicola Douglass; Michiel T van Diepen; Rosamund Chapman; Shireen Galant; Emmanuel Margolin; Phindile Ximba; Tandile Hermanus; Penny L Moore; Anna-Lise Williamson

doi:10.1016/j.vaccine.2020.12.024

Modifications to the HIV-1 SAAVI MVA-C vaccine improve in vitro expression and in vivo immunogenicity

Vaccine. 2021 Jan 15;39(3):463-468. doi: 10.1016/j.vaccine.2020.12.024. Epub 2020 Dec 17.

Authors

Nicola Douglass¹, Michiel T van Diepen², Rosamund Chapman², Shireen Galant², Emmanuel Margolin³, Phindile Ximba², Tandile Hermanus⁴, Penny L Moore⁵, Anna-Lise Williamson²

Affiliations

¹ Division of Medical Virology, Department of Pathology, University of Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa. Electronic address: Niki.Douglass@uct.ac.za.
² Division of Medical Virology, Department of Pathology, University of Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa.
³ Division of Medical Virology, Department of Pathology, University of Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa; Wellcome Trust Centre for Infectious Disease Research in Africa, University of Cape Town, South Africa; Biopharming Research Unit, Department of Molecular and Cell Biology, University of Cape Town, South Africa.
⁴ Centre for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa; Antibody Immunity Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁵ Centre for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa; Antibody Immunity Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Congella, Durban, South Africa.

PMID: 33342638
DOI: 10.1016/j.vaccine.2020.12.024

Abstract

Two HIV-1 vaccines (SAAVI DNA-C2 and SAAVI MVA-C) were previously developed in South Africa and tested in preclinical studies and Phase 1 clinical trials. Here we report on improvements made to the SAAVI MVA-C vaccine design which include: the use of different promoters for both the Gag and Env genes, replacement of the native Gag gene with an in silico designed subtype C mosaic Gag antigen which forms virus-like particles and the modification of Env by sequence changes to improve stability and transport to the cell surface. A head-to-head comparison of the newly conceived MVAGD5 candidate vaccine with SAAVI MVA-C showed increased in vitro expression of both Env and Gag, and superior immunogenicity in rabbits. MVAGD5 induced high levels of binding antibodies to Env and Tier 1A and 1B neutralizing antibodies, neither of which were induced by SAAVI MVA-C.

Keywords: Env; Gag mosaic; HIV-1 vaccines; Immunogenicity; MVA; Neutralization.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

AIDS Vaccines*
Animals
HIV Antibodies
HIV-1* / genetics
Immunization, Secondary
Rabbits
South Africa
Vaccines, DNA*

Substances

AIDS Vaccines
HIV Antibodies
Vaccines, DNA

Grants and funding

108473/Z/15/Z/WT_/Wellcome Trust/United Kingdom