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.
Highlights
We evaluate preclinically a mosaic/epigraph mRNA vaccine delivering the second-generation tetravalent conserved regions of HIV-1 and demonstrate robust T-cell immunogenicity
872 amino acids, or 28% ofwhich the HIV-1 of beneficial regionstwo. These werePol computed into two complementing mosaics, together proteome, were selected for their high conservation among the HIV-1 group isolates and inclusion achieved over 80% match of potential 9-mer T-cell epitopes over most of the six HIVconsvX
Keeping in mind some experimental differences, the summed magnitude of T-cell responses reported here is superior to our published data for the bivalent HIVconsvX vaccine delivered using adjuvanted Semliki Forest virus-derived self-amplifying mRNA [17]
Summary
To this end, we demonstrated in a series of phase 1 and 2 clinical trials induction of broadly specific T cells targeting conserved regions of HIV-1. We demonstrated in a series of phase 1 and 2 clinical trials induction of broadly specific T cells targeting conserved regions of HIV-1 These T cells inhibited viruses representative of four major clades and provided a signal of a durable virus control after stopping antiretroviral treatment (ART) in patients treated during primary HIV-1 infection [11,12,13,14]. We evaluate preclinically a mosaic/epigraph mRNA vaccine delivering the second-generation tetravalent conserved regions of HIV-1 and demonstrate robust T-cell immunogenicity
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