Characterization of HIV-1 Nucleoside-Modified mRNA Vaccines in Rabbits and Rhesus Macaques.

Published

Journal Article

Despite the enormous effort in the development of effective vaccines against HIV-1, no vaccine candidate has elicited broadly neutralizing antibodies in humans. Thus, generation of more effective anti-HIV vaccines is critically needed. Here we characterize the immune responses induced by nucleoside-modified and purified mRNA-lipid nanoparticle (mRNA-LNP) vaccines encoding the clade C transmitted/founder HIV-1 envelope (Env) 1086C. Intradermal vaccination with nucleoside-modified 1086C Env mRNA-LNPs elicited high levels of gp120-specific antibodies in rabbits and rhesus macaques. Antibodies generated in rabbits neutralized a tier 1 virus, but no tier 2 neutralization activity could be measured. Importantly, three of six non-human primates developed antibodies that neutralized the autologous tier 2 strain. Despite stable anti-gp120 immunoglobulin G (IgG) levels, tier 2 neutralization titers started to drop 4 weeks after booster immunizations. Serum from both immunized rabbits and non-human primates demonstrated antibody-dependent cellular cytotoxicity activity. Collectively, these results are supportive of continued development of nucleoside-modified and purified mRNA-LNP vaccines for HIV. Optimization of Env immunogens and vaccination protocols are needed to increase antibody neutralization breadth and durability.

Full Text

Duke Authors

Cited Authors

  • Pardi, N; LaBranche, CC; Ferrari, G; Cain, DW; Tombácz, I; Parks, RJ; Muramatsu, H; Mui, BL; Tam, YK; Karikó, K; Polacino, P; Barbosa, CJ; Madden, TD; Hope, MJ; Haynes, BF; Montefiori, DC; Hu, S-L; Weissman, D

Published Date

  • April 2019

Published In

Volume / Issue

  • 15 /

Start / End Page

  • 36 - 47

PubMed ID

  • 30974332

Pubmed Central ID

  • 30974332

Electronic International Standard Serial Number (EISSN)

  • 2162-2531

International Standard Serial Number (ISSN)

  • 2162-2531

Digital Object Identifier (DOI)

  • 10.1016/j.omtn.2019.03.003

Language

  • eng