There is a great need for the development of vaccines that induce potent and long-lasting protective immunity against SARS-CoV-2. Multimeric display of the antigen combined with potent adjuvant can enhance the potency and longevity of the antibody response. The receptor binding domain (RBD) of the spike protein is a primary target of neutralizing antibodies. Here, we developed a trimeric form of the RBD and show that it induces a potent neutralizing antibody response against live virus with diverse effector functions and provides protection against SARS-CoV-2 challenge in mice and rhesus macaques. The trimeric form induces higher neutralizing antibody titer compared to monomer with as low as 1μg antigen dose. In mice, adjuvanting the protein with a TLR7/8 agonist formulation alum-3M-052 induces 100-fold higher neutralizing antibody titer and superior protection from infection compared to alum. SARS-CoV-2 infection causes significant loss of innate cells and pathology in the lung, and vaccination protects from changes in innate cells and lung pathology. These results demonstrate RBD trimer protein as a suitable candidate for vaccine against SARS-CoV-2. Efficient vaccines for SARS-CoV-2 are needed. Here, the authors show that a trimeric form of the receptor-binding domain of SARS-CoV-2 spike adjuvanted with alum-3M-052 protects non-human primates from disease and inhibits infection.
【저자키워드】 SARS-CoV-2, viral infection, Protein vaccines, 【초록키워드】 pathology, Vaccine, vaccination, Neutralizing antibodies, SARS-COV-2 infection, Antibody Response, Infection, TLR7, lung, Spike protein, Receptor binding domain, Antigen, Protein, Receptor-binding domain, protective immunity, mice, RBD, non-human primates, Antibody titer, Longevity, non-human primate, disease, efficient, function, Neutralizing antibody response, Live virus, Neutralizing antibody titer, SARS-CoV-2 spike, rhesus macaques, Lung pathology, dose, alum, potency, TLR7/8, trimer, monomer, trimeric, ENhance, PROTECT, inhibit, provide, changes in, the spike protein, long-lasting, the RBD, the receptor-binding domain, induce, cause, the antibody response, innate cell, 【제목키워드】 immune, Protein, PROTECT, SARS-CoV-2 RBD trimer,