Needle-Free Devices and CpG-Adjuvanted DNA Improve Anti-HIV Antibody Responses of Both DNA and Modified Vaccinia Ankara-Vectored Candidate Vaccines

Author:

Chapman Rosamund12ORCID,van Diepen Michiel12,Douglass Nicola12ORCID,Hermanus Tandile34,Moore Penny L.345,Williamson Anna-Lise12ORCID

Affiliation:

1. Institute of Infectious Disease and Molecular Medicine, Faculty of Health Science, University of Cape Town, Cape Town 7925, South Africa

2. Division of Medical Virology, Department of Pathology, University of Cape Town, Cape Town 7925, South Africa

3. Centre for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa

4. Antibody Immunity Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2050, South Africa

5. Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Congella, Durban 4013, South Africa

Abstract

The combination of mosaic Gag and CAP256 envelope in an HIV vaccine regimen comprising DNA prime and modified vaccinia Ankara (MVA) boost followed by protein boost has previously been shown to generate robust autologous Tier 2 neutralizing antibodies (nAbs) in rabbits. Further refinements of this strategy have been investigated to improve antibody responses. The delivery of both DNA and recombinant MVA vaccines with a needle-free device was compared to delivery by injection, and the effect of formulating the DNA vaccine with adjuvant CpG ODN 1826 was determined. The Pharmajet Stratis® needle-free injection device (PharmaJet, Golden, CO, USA) improved binding antibody responses to the DNA vaccine as well as both binding and neutralizing antibody responses to the MVA vaccines. Formulation of the DNA vaccines with CpG adjuvant further improved the antibody responses. A shortened vaccination regimen of a single DNA inoculation followed by a single MVA inoculation did not elicit Tier 1B nor Tier 2 neutralization responses as produced by the two DNA, followed by two MVA vaccination regimen. This study showed the immunogenicity of HIV DNA and MVA vaccines administered in a DDMM regimen could be improved using the PharmaJet Stratis needle-free injection device and formulation of the DNA vaccines with CpG adjuvant.

Funder

South African Medical Research Council

National Research Foundation

Publisher

MDPI AG

Subject

Pharmacology (medical),Infectious Diseases,Drug Discovery,Pharmacology,Immunology

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