SARS-CoV-2 RBD trimer protein adjuvanted with Alum-3M-052 protects from SARS-CoV-2 infection and immune pathology in the lung
Autor: | Mehul S. Suthar, Sailaja Gangadhara, Shannon Kirejczyk, Vineet D. Menachery, Narayanaiah Cheedarla, Venkata Viswanadh Edara, Sally Shin, Venkata S. Bollimpelli, Stephanie Fischinger, Katharine Floyd, Caroline Atyeo, Anusmita Sahoo, Pei Yong Shi, Kenneth H. Dinnon, Rama Rao Amara, Christopher B. Fox, Thomas H. Vanderford, Lilin Lai, Galit Alter, Lisa E. Gralinski, Tiffany M. Styles, Sanjeev Gumber, Ayalnesh Shiferaw, Mark A. Tomai, Nanda Kishore Routhu |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Pathology viruses medicine.medical_treatment General Physics and Astronomy Antibodies Viral Mice 0302 clinical medicine 030212 general & internal medicine skin and connective tissue diseases Neutralizing antibody Multidisciplinary biology Vaccination Titer Spike Glycoprotein Coronavirus Alum Compounds Angiotensin-Converting Enzyme 2 Antibody Heterocyclic Compounds 3-Ring Adjuvant Stearic Acids Protein Binding Protein vaccines medicine.medical_specialty COVID-19 Vaccines Science Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Immune system Adjuvants Immunologic Antigen medicine Animals Humans SARS-CoV-2 fungi COVID-19 General Chemistry TLR7 Antibodies Neutralizing Macaca mulatta respiratory tract diseases body regions Disease Models Animal 030104 developmental biology Viral infection Antibody Formation biology.protein |
Zdroj: | Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-15 (2021) |
ISSN: | 2041-1723 |
Popis: | 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. Efficient vaccines for SARS-CoV-2 are needed. Here, the authors show that a trimeric form of the receptor-binding domain of SARS-CoV-2 spike adjuvanted with alum-3M-052 protects non-human primates from disease and inhibits infection. |
Databáze: | OpenAIRE |
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