Low-dose self-amplifying mRNA COVID-19 vaccine drives strong protective immunity in non-human primates against SARS-CoV-2 infection.

Autor: Rappaport AR; Gritstone bio, Inc., Emeryville, CA, USA., Hong SJ; Gritstone bio, Inc., Emeryville, CA, USA., Scallan CD; Gritstone bio, Inc., Emeryville, CA, USA., Gitlin L; Gritstone bio, Inc., Emeryville, CA, USA., Akoopie A; Gritstone bio, Inc., Emeryville, CA, USA., Boucher GR; Gritstone bio, Inc., Emeryville, CA, USA., Egorova M; Gritstone bio, Inc., Emeryville, CA, USA., Espinosa JA; Gritstone bio, Inc., Emeryville, CA, USA., Fidanza M; Gritstone bio, Inc., Emeryville, CA, USA., Kachura MA; Gritstone bio, Inc., Emeryville, CA, USA., Shen A; Gritstone bio, Inc., Emeryville, CA, USA., Sivko G; Battelle Biomedical Research Center, West Jefferson, OH, USA., Van Abbema A; Gritstone bio, Inc., Emeryville, CA, USA., Veres RL; Gritstone bio, Inc., Emeryville, CA, USA., Jooss K; Gritstone bio, Inc., Emeryville, CA, USA. kjooss@gritstone.com.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Jun 07; Vol. 13 (1), pp. 3289. Date of Electronic Publication: 2022 Jun 07.
DOI: 10.1038/s41467-022-31005-z
Abstrakt: The coronavirus disease 2019 (COVID-19) pandemic continues to spread globally, highlighting the urgent need for safe and effective vaccines that could be rapidly mobilized to immunize large populations. We report the preclinical development of a self-amplifying mRNA (SAM) vaccine encoding a prefusion stabilized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein and demonstrate strong cellular and humoral immune responses at low doses in mice and rhesus macaques. The homologous prime-boost vaccination regimen of SAM at 3, 10 and 30 μg induced potent neutralizing antibody (nAb) titers in rhesus macaques following two SAM vaccinations at all dose levels, with the 10 μg dose generating geometric mean titers (GMT) 48-fold greater than the GMT of a panel of SARS-CoV-2 convalescent human sera. Spike-specific T cell responses were observed with all tested vaccine regimens. SAM vaccination provided protective efficacy against SARS-CoV-2 challenge as both a homologous prime-boost and as a single boost following ChAd prime, demonstrating reduction of viral replication in both the upper and lower airways. The SAM vaccine is currently being evaluated in clinical trials as both a homologous prime-boost regimen at low doses and as a boost following heterologous prime.
(© 2022. The Author(s).)
Databáze: MEDLINE
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