Tetravalent Immunogen Assembled from Conserved Regions of HIV-1 and Delivered as mRNA Demonstrates Potent Preclinical T-Cell Immunogenicity and Breadth
The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK
Los Alamo National Laboratory, Theoretical Biology and Biophysics, Los Alamos, NM 87545, USA
New Mexico Consortium, Los Alamos, NM 87545, USA
Moderna Inc., Cambridge, MA 02139, USA
International AIDS Vaccine Initiative-New York, New York, NY 10004, USA
Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto 860-0811, Japan
Author to whom correspondence should be addressed.
Vaccines 2020, 8(3), 360; https://doi.org/10.3390/vaccines8030360
Received: 5 June 2020 / Revised: 1 July 2020 / Accepted: 2 July 2020 / Published: 6 July 2020
(This article belongs to the Section HIV Vaccines)
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.