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 Satish Bollimpelli, Sailaja Gangadhara, Venkata Viswanadh Edara, Lilin Lai, Anusmita Sahoo, Ayalnesh Shiferaw, Tiffany M. Styles, Katharine Floyd, Stephanie Fischinger, Caroline Atyeo, Sally A. Shin, Sanjeev Gumber, Shannon Kirejczyk, Kenneth H. Dinnon, Pei-Yong Shi, Vineet D. Menachery, Mark Tomai, Christopher B. Fox, Galit Alter, Thomas H. Vanderford, Lisa Gralinski, Mehul S. Suthar and Rama Rao Amara ()
Additional contact information
Nanda Kishore Routhu: Emory University
Narayanaiah Cheedarla: Emory University
Venkata Satish Bollimpelli: Emory University
Sailaja Gangadhara: Emory University
Venkata Viswanadh Edara: Emory University
Lilin Lai: Emory University
Anusmita Sahoo: Emory University
Ayalnesh Shiferaw: Emory University
Tiffany M. Styles: Emory University
Katharine Floyd: Emory University
Stephanie Fischinger: MIT and Harvard
Caroline Atyeo: MIT and Harvard
Sally A. Shin: MIT and Harvard
Sanjeev Gumber: Emory University
Shannon Kirejczyk: Emory University
Kenneth H. Dinnon: University of North Carolina
Pei-Yong Shi: The University of Texas Medical Branch
Vineet D. Menachery: The University of Texas Medical Branch
Mark Tomai: 3M Corporate Research Materials Laboratory
Christopher B. Fox: Infectious Disease Research Institute
Galit Alter: MIT and Harvard
Thomas H. Vanderford: Emory University
Lisa Gralinski: University of North Carolina
Mehul S. Suthar: Emory University
Rama Rao Amara: Emory University

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-23942-y

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