Achieving sufficient worldwide vaccination coverage against SARS-CoV-2 will require additional approaches to currently approved viral vector and mRNA vaccines. Subunit vaccines may have distinct advantages when immunizing vulnerable individuals, children and pregnant women. Here, we present a new generation of subunit vaccines targeting viral antigens to CD40-expressing antigen-presenting cells. We demonstrate that targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein to CD40 (αCD40.RBD) induces significant levels of specific T and B cells, with long-term memory phenotypes, in a humanized mouse model. Additionally, we demonstrate that a single dose of the αCD40.RBD vaccine, injected without adjuvant, is sufficient to boost a rapid increase in neutralizing antibodies in convalescent non-human primates (NHPs) exposed six months previously to SARS-CoV-2. Vaccine-elicited antibodies cross-neutralize different SARS-CoV-2 variants, including D614G, B1.1.7 and to a lesser extent B1.351. Such vaccination significantly improves protection against a new high-dose virulent challenge versus that in non-vaccinated convalescent animals. In this study, Marlin et al. provide insights into the potential use of subunit vaccines that induce a high level of protection against SARS-CoV-2 in animal models.
【저자키워드】 SARS-CoV-2, viral infection, Protein vaccines, Preclinical research, 【초록키워드】 neutralizing antibody, Viral vector, Vaccine, vaccination, Neutralizing antibodies, antibody, children, B cells, animal models, Spike protein, mRNA vaccines, memory, pregnant women, Coverage, Viral, Receptor-binding domain, SARS-CoV-2 variants, RBD, NHPs, SARS-CoV-2 spike protein, D614G, Subunit vaccine, adjuvant, convalescent, non-human primate, boost, single dose, cross-neutralize, subunit vaccines, T and B cells, long-term memory, Phenotypes, High-dose, Viral antigen, antigen-presenting cells, viral antigens, rapid increase, CD40, viral vector and mRNA vaccines, significant level, virulent, B1.351, humanized, approach, IMPROVE, significantly, approved, injected, the receptor-binding domain, induce, individuals, Marlin, the SARS-CoV-2, 【제목키워드】 Infection, macaque, convalescent, domain, targeting, Cell, IMPROVE, expressing,