Details

Autor(en) / Beteiligte

• Pardi, Norbert
• LaBranche, Celia C.
• Ferrari, Guido
• Cain, Derek W.
• Tombácz, István
• Parks, Robert J.
• Muramatsu, Hiromi
• Mui, Barbara L.
• Tam, Ying K.
• Karikó, Katalin
• Polacino, Patricia
• Barbosa, Christopher J.
• Madden, Thomas D.
• Hope, Michael J.
• Haynes, Barton F.
• Montefiori, David C.
• Hu, Shiu-Lok
• Weissman, Drew

Titel

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

Ist Teil von

• Molecular therapy. Nucleic acids, 2019-04, Vol.15, p.36-47

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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.