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Adjuvanting a subunit COVID-19 vaccine to induce protective immunity
- Source :
- Nature. June 10, 2021, Vol. 594 Issue 7862, p253, 6 p.
- Publication Year :
- 2021
-
Abstract
- The development of a portfolio of COVID-19 vaccines to vaccinate the global population remains an urgent public health imperative.sup.1. Here we demonstrate the capacity of a subunit vaccine, comprising the SARS-CoV-2 spike protein receptor-binding domain displayed on an I53-50 protein nanoparticle scaffold (hereafter designated RBD-NP), to stimulate robust and durable neutralizing-antibody responses and protection against SARS-CoV-2 in rhesus macaques. We evaluated five adjuvants including Essai O/W 1849101, a squalene-in-water emulsion; AS03, an [alpha]-tocopherol-containing oil-in-water emulsion; AS37, a Toll-like receptor 7 (TLR7) agonist adsorbed to alum; CpG1018-alum, a TLR9 agonist formulated in alum; and alum. RBD-NP immunization with AS03, CpG1018-alum, AS37 or alum induced substantial neutralizing-antibody and CD4 T cell responses, and conferred protection against SARS-CoV-2 infection in the pharynges, nares and bronchoalveolar lavage. The neutralizing-antibody response to live virus was maintained up to 180 days after vaccination with RBD-NP in AS03 (RBD-NP-AS03), and correlated with protection from infection. RBD-NP immunization cross-neutralized the B.1.1.7 SARS-CoV-2 variant efficiently but showed a reduced response against the B.1.351 variant. RBD-NP-AS03 produced a 4.5-fold reduction in neutralization of B.1.351 whereas the group immunized with RBD-NP-AS37 produced a 16-fold reduction in neutralization of B.1.351, suggesting differences in the breadth of the neutralizing-antibody response induced by these adjuvants. Furthermore, RBD-NP-AS03 was as immunogenic as a prefusion-stabilized spike immunogen (HexaPro) with AS03 adjuvant. These data highlight the efficacy of the adjuvanted RBD-NP vaccine in promoting protective immunity against SARS-CoV-2 and have led to phase I/II clinical trials of this vaccine (NCT04742738 and NCT04750343). Trials in rhesus macaques show that a subunit vaccine against SARS-CoV-2, comprising the spike protein receptor-binding domain displayed on a nanoparticle protein scaffold, produces a robust protective response against the virus.<br />Author(s): Prabhu S. Arunachalam [sup.1] , Alexandra C. Walls [sup.2] , Nadia Golden [sup.3] , Caroline Atyeo [sup.4] , Stephanie Fischinger [sup.4] , Chunfeng Li [sup.1] , Pyone Aye [sup.3] [...]
- Subjects :
- Environmental issues
Science and technology
Zoology and wildlife conservation
Subjects
Details
- Language :
- English
- ISSN :
- 00280836
- Volume :
- 594
- Issue :
- 7862
- Database :
- Gale General OneFile
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.664722351
- Full Text :
- https://doi.org/10.1038/s41586-021-03530-2