TY - JOUR
T1 - 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
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85107654742&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-23942-y
DO - 10.1038/s41467-021-23942-y
M3 - Article
C2 - 34117252
AN - SCOPUS:85107654742
SN - 2041-1723
VL - 12
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 3587
ER -