Research ArticleCORONAVIRUS

An Alphavirus-derived replicon RNA vaccine induces SARS-CoV-2 neutralizing antibody and T cell responses in mice and nonhuman primates

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Science Translational Medicine  05 Aug 2020:
Vol. 12, Issue 555, eabc9396
DOI: 10.1126/scitranslmed.abc9396

A replicating RNA vaccine candidate to fight COVID-19

The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 is having a major global public health impact necessitating the rapid development of an effective vaccine. Erasmus et al. report that a replicating RNA vaccine stabilized in a lipid inorganic nanoparticle (LION) formulation induced robust antibody responses after a single intramuscular immunization in mice and after a single intramuscular injection at five different sites in macaques. These antibodies neutralized SARS-CoV-2 at titers comparable to those reported in humans convalescing from COVID-19. Prime/boost vaccination of mice and macaques also induced T cell responses that could potentially contribute to protection. This RNA vaccine also induced robust immune responses in aged mice, suggesting the potential for protection in the elderly. These findings support further development of this COVID-19 vaccine candidate.

Abstract

The coronavirus disease 2019 (COVID-19) pandemic, caused by infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is having a deleterious impact on health services and the global economy, highlighting the urgent need for an effective vaccine. Such a vaccine would need to rapidly confer protection after one or two doses and would need to be manufactured using components suitable for scale up. Here, we developed an Alphavirus-derived replicon RNA vaccine candidate, repRNA-CoV2S, encoding the SARS-CoV-2 spike (S) protein. The RNA replicons were formulated with lipid inorganic nanoparticles (LIONs) that were designed to enhance vaccine stability, delivery, and immunogenicity. We show that a single intramuscular injection of the LION/repRNA-CoV2S vaccine in mice elicited robust production of anti–SARS-CoV-2 S protein IgG antibody isotypes indicative of a type 1 T helper cell response. A prime/boost regimen induced potent T cell responses in mice including antigen-specific responses in the lung and spleen. Prime-only immunization of aged (17 months old) mice induced smaller immune responses compared to young mice, but this difference was abrogated by booster immunization. In nonhuman primates, prime-only immunization in one intramuscular injection site or prime/boost immunizations in five intramuscular injection sites elicited modest T cell responses and robust antibody responses. The antibody responses persisted for at least 70 days and neutralized SARS-CoV-2 at titers comparable to those in human serum samples collected from individuals convalescing from COVID-19. These data support further development of LION/repRNA-CoV2S as a vaccine candidate for prophylactic protection against SARS-CoV-2 infection.

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