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

Publication ,  Journal Article
Pardi, N; LaBranche, CC; Ferrari, G; Cain, DW; Tombácz, I; Parks, RJ; Muramatsu, H; Mui, BL; Tam, YK; Karikó, K; Polacino, P; Barbosa, CJ ...
Published in: Mol Ther Nucleic Acids
April 15, 2019

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.

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Published In

Mol Ther Nucleic Acids

DOI

ISSN

2162-2531

Publication Date

April 15, 2019

Volume

15

Start / End Page

36 / 47

Location

United States

Related Subject Headings

  • 3101 Biochemistry and cell biology
  • 1103 Clinical Sciences
  • 0601 Biochemistry and Cell Biology
 

Citation

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Pardi, N., LaBranche, C. C., Ferrari, G., Cain, D. W., Tombácz, I., Parks, R. J., … Weissman, D. (2019). Characterization of HIV-1 Nucleoside-Modified mRNA Vaccines in Rabbits and Rhesus Macaques. Mol Ther Nucleic Acids, 15, 36–47. https://doi.org/10.1016/j.omtn.2019.03.003
Pardi, Norbert, Celia C. LaBranche, Guido Ferrari, Derek W. Cain, István Tombácz, Robert J. Parks, Hiromi Muramatsu, et al. “Characterization of HIV-1 Nucleoside-Modified mRNA Vaccines in Rabbits and Rhesus Macaques.Mol Ther Nucleic Acids 15 (April 15, 2019): 36–47. https://doi.org/10.1016/j.omtn.2019.03.003.
Pardi N, LaBranche CC, Ferrari G, Cain DW, Tombácz I, Parks RJ, et al. Characterization of HIV-1 Nucleoside-Modified mRNA Vaccines in Rabbits and Rhesus Macaques. Mol Ther Nucleic Acids. 2019 Apr 15;15:36–47.
Pardi, Norbert, et al. “Characterization of HIV-1 Nucleoside-Modified mRNA Vaccines in Rabbits and Rhesus Macaques.Mol Ther Nucleic Acids, vol. 15, Apr. 2019, pp. 36–47. Pubmed, doi:10.1016/j.omtn.2019.03.003.
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. Characterization of HIV-1 Nucleoside-Modified mRNA Vaccines in Rabbits and Rhesus Macaques. Mol Ther Nucleic Acids. 2019 Apr 15;15:36–47.
Journal cover image

Published In

Mol Ther Nucleic Acids

DOI

ISSN

2162-2531

Publication Date

April 15, 2019

Volume

15

Start / End Page

36 / 47

Location

United States

Related Subject Headings

  • 3101 Biochemistry and cell biology
  • 1103 Clinical Sciences
  • 0601 Biochemistry and Cell Biology