TY - JOUR TI - SARS-CoV-2 RBD trimer protein adjuvanted with Alum-3M-052 protects from SARS-CoV-2 infection and immune pathology in the lung AU - Routhu, Nanda Kishore AU - Cheedarla, Narayanaiah AU - Bollimpelli, Venkata Satish AU - Gangadhara, Sailaja AU - Edara, Venkata Viswanadh AU - Lai, Lilin AU - Sahoo, Anusmita AU - Shiferaw, Ayalnesh AU - Styles, Tiffany M. AU - Floyd, Katharine AU - Fischinger, Stephanie AU - Atyeo, Caroline AU - Shin, Sally A. AU - Gumber, Sanjeev AU - Kirejczyk, Shannon AU - Dinnon, Kenneth H. AU - Shi, Pei-Yong AU - Menachery, Vineet D. AU - Tomai, Mark AU - Fox, Christopher B. AU - Alter, Galit AU - Vanderford, Thomas H. AU - Gralinski, Lisa AU - Suthar, Mehul S. AU - Amara, Rama Rao T2 - Nature Communications AB - 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. DA - 2021/06/11/ PY - 2021 DO - 10.1038/s41467-021-23942-y DP - www.nature.com VL - 12 IS - 1 SP - 3587 J2 - Nat Commun LA - en SN - 2041-1723 UR - https://www.nature.com/articles/s41467-021-23942-y Y2 - 2021/06/11/22:21:40 ER -