Author: Routhu, Nanda Kishore; Cheedarla, Narayanaiah; Bollimpelli, Venkata Satish; Gangadhara, Sailaja; Edara, Venkata Viswanadh; Lai, Lilin; Sahoo, Anusmita; Shiferaw, Ayalnesh; Styles, Tiffany M.; Floyd, Katharine; Fischinger, Stephanie; Atyeo, Caroline; Shin, Sally A.; Gumber, Sanjeev; Kirejczyk, Shannon; Dinnon, Kenneth H.; Shi, Pei-Yong; Menachery, Vineet D.; Tomai, Mark; Fox, Christopher B.; Alter, Galit; Vanderford, Thomas H.; Gralinski, Lisa; Suthar, Mehul S.; Amara, Rama Rao
Title: SARS-CoV-2 RBD trimer protein adjuvanted with Alum-3M-052 protects from SARS-CoV-2 infection and immune pathology in the lung Cord-id: 1bn6rmli Document date: 2021_6_11
ID: 1bn6rmli
Snippet: 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 dive
Document: 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.
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