Tetravalent Immunogen Assembled from Conserved Regions of HIV-1 and Delivered As MRNA Demonstrates Potent Preclinical T-Cell Immunogenicity and Breadth

Overview

Journal Vaccines (Basel)

Date 2020 Jul 10

PMID 32640600

Citations 12

Authors

Nathifa Moyo

Edmund G Wee

Bette Korber

Kapil Bahl

Samantha Falcone

Sunny Himansu

Adrianne L Wong

Antu K Dey

Mark Feinberg

Tomas Hanke

Affiliations

Soon will be listed here.

Abstract

A vaccine will likely be one of the key tools for ending the HIV-1/AIDS epidemic by preventing HIV-1 spread within uninfected populations and achieving a cure for people living with HIV-1. The currently prevailing view of the vaccine field is to introduce protective antibodies, nevertheless, a vaccine to be effective may need to harness protective T cells. We postulated that focusing a T-cell response on the most vulnerable regions of the HIV-1 proteome while maximizing a perfect match between the vaccine and circulating viruses will control HIV-1 replication. We currently use a combination of replication-deficient simian (chimpanzee) adenovirus and poxvirus modified vaccinia virus Ankara to deliver bivalent conserved-mosaic immunogens to human volunteers. Here, we exploit the mRNA platform by designing tetravalent immunogens designated as HIVconsvM, and demonstrate that mRNA formulated in lipid nanoparticles induces potent, broad and polyfunctional T-cell responses in a pre-clinical model. These results support optimization and further development of this vaccine strategy in experimental medicine trials in humans.

Citing Articles

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