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.
Medical Subject Headings: skin and connective tissue diseasesfungibody regions
free text keywords: [SDV]Life Sciences [q-bio], General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Science, Q, Article, Viral infection, Protein vaccines, SARS-CoV-2, Preclinical research, Adjuvant, medicine.medical_treatment, medicine, Protein domain, Antibody, biology.protein, biology, Viral vector, Virology, CD40, Humanized mouse, Virulence, Vaccination