SARS-CoV-2 RBD trimer protein adjuvanted with Alum-3M-052 protects from SARS-CoV-2 infection and immune pathology in the lung
Nanda Kishore Routhu, Narayanaiah Cheedarla, Venkata S. Bollimpelli, Sailaja Gangadhara, Venkata Viswanadh Edara, Lilin Lai, Anusmita Sahoo, Ayalnesh Shiferaw, Tiffany M. Styles, Katharine Floyd, Stephanie Fischinger, Caroline Atyeo, Sally Shin, Sanjeev Gumber, Shannon G. M. Kirejczyk, Kenneth H. Dinnon, Pei‐Yong Shi, Vineet D. Menachery, Mark A. Tomai, Christopher B. Fox, Galit Alter, Thomas H. Vanderford, Lisa E. Gralinski, Mehul S. Suthar, Rama Rao Amara
Abstract
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.