Immunogenicity of a cold-chain friendly and long-term stable HIV multi-epitope protease cleavage sites (MEPCS)-mRNA-LNP vaccine.

Abstract The failure of HIV vaccine clinical trials calls for novel vaccine development strategies. Studies on HIV highly exposed seronegative sex workers showed that focused virus-specific CD8+ T-cell responses are associated with the protection. Following the unconventional HIV vaccine approach targeting 12 highly conserved sequences surrounding the protease cleavage sites (PCS), we designed multi-epitope PCS mRNA-loaded lipid nanoparticles (MEPCS-mRNA-LNP) to promote more efficient antigen presentation. The modified LNP formulation produced stable and cold-chain-friendly MEPCS-mRNA-LNP. The mice study showed the vaccinated group generates PCS-specific CD8+ memory T-cells with cytotoxic function, both systemically and at the HIV-targeted tissue sites (like HESN group), with T-polyfunctional response. As expected, little to no significant activation of CD4+ T-cells was observed. The proof-of-concept study indicates that the MEPCS-mRNA LNP vaccine approach induces immunological memory against highly conserved HIV pro-polyprotein (limiting HIV’s mutability). The MEPCS-mRNA LNP vaccine could be a potential candidate for an effective prophylactic HIV vaccine.