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

Vaccines

AntuK. Dey¹  AdrianneL. Wong¹  Mark Feinberg¹  Bette Korber²  Kapil Bahl³  Samantha Falcone³  Sunny Himansu³  Tomáš Hanke⁴  Nathifa Moyo⁴  EdmundG. Wee⁴ 

[1] International AIDS Vaccine Initiative-New York, New York, NY 10004, USA;Los Alamo National Laboratory, Theoretical Biology and Biophysics, Los Alamos, NM 87545, USA;Moderna Inc., Cambridge, MA 02139, USA;The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK;

关键词: HIV vaccine;    HIVconsvX;    HIVconsv;    conserved regions;    T cell vaccine;    mRNA vaccines;   

DOI  :  10.3390/vaccines8030360

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown