| Literature DB >> 34887575 |
Peng Zhang1, Elisabeth Narayanan2, Qingbo Liu1, Yaroslav Tsybovsky3, Kristin Boswell4, Shilei Ding5, Zonghui Hu6, Dean Follmann6, Yin Lin1, Huiyi Miao1, Hana Schmeisser1, Denise Rogers1, Samantha Falcone2, Sayda M Elbashir2, Vladimir Presnyak2, Kapil Bahl2, Madhu Prabhakaran4, Xuejun Chen4, Edward K Sarfo4, David R Ambrozak4, Rajeev Gautam7, Malcom A Martin7, Joanna Swerczek8, Richard Herbert8, Deborah Weiss9, Johnathan Misamore9, Giuseppe Ciaramella2, Sunny Himansu2, Guillaume Stewart-Jones2, Adrian McDermott4, Richard A Koup4, John R Mascola4, Andrés Finzi5, Andrea Carfi2, Anthony S Fauci1, Paolo Lusso10.
Abstract
The development of a protective vaccine remains a top priority for the control of the HIV/AIDS pandemic. Here, we show that a messenger RNA (mRNA) vaccine co-expressing membrane-anchored HIV-1 envelope (Env) and simian immunodeficiency virus (SIV) Gag proteins to generate virus-like particles (VLPs) induces antibodies capable of broad neutralization and reduces the risk of infection in rhesus macaques. In mice, immunization with co-formulated env and gag mRNAs was superior to env mRNA alone in inducing neutralizing antibodies. Macaques were primed with a transmitted-founder clade-B env mRNA lacking the N276 glycan, followed by multiple booster immunizations with glycan-repaired autologous and subsequently bivalent heterologous envs (clades A and C). This regimen was highly immunogenic and elicited neutralizing antibodies against the most prevalent (tier-2) HIV-1 strains accompanied by robust anti-Env CD4+ T cell responses. Vaccinated animals had a 79% per-exposure risk reduction upon repeated low-dose mucosal challenges with heterologous tier-2 simian-human immunodeficiency virus (SHIV AD8). Thus, the multiclade env-gag VLP mRNA platform represents a promising approach for the development of an HIV-1 vaccine.Entities:
Mesh：
Substances：
Year: 2021 PMID： 34887575 DOI： 10.1038/s41591-021-01574-5
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440