期刊
NATURE MEDICINE
卷 27, 期 12, 页码 2234-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41591-021-01574-5
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资金
- Intramural Research Program of the Division of Intramural Research
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH
- NIH Office of AIDS Research
- Bill and Melinda Gates Foundation
- Frederick National Laboratory for Cancer Research, NIH [HHSN261200800001]
An mRNA vaccine platform showed promising results in generating broadly neutralizing antibodies in non-human primates and reducing the risk of infection, highlighting its potential for developing an effective HIV-1 vaccine.
An mRNA vaccine platform to prevent HIV-1 infection generated broadly neutralizing antibodies in non-human primates and protected some animals from infection, raising hope that optimization of this approach might lead to an effective HIV vaccine. 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.
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