SARS-CoV-2 RBD trimer protein adjuvanted with Alum-3M-052 protects from SARS-CoV-2 infection and immune pathology in the lung.

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.

• Authors: 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 3rd, Pei-Yong Shi, Vineet D Menachery, Mark Tomai, Christopher B Fox, Galit Alter, Thomas H Vanderford, Lisa Gralinski, Mehul S Suthar, Rama Rao Amara
• Journal: Nature communications (Nat Commun) Vol. 12 Issue 1 Pg. 3587 (06 11 2021) ISSN: 2041-1723 [Electronic] England
• PMID: 34117252 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Alum Compounds
• Antibodies, Neutralizing
• Antibodies, Viral
• COVID-19 Vaccines
• Heterocyclic Compounds, 3-Ring
• Spike Glycoprotein, Coronavirus
• Stearic Acids
• spike protein, SARS-CoV-2
• MEDI9197
• aluminum sulfate
• Angiotensin-Converting Enzyme 2

Topics

• Adjuvants, Immunologic (administration & dosage)
• Alum Compounds (administration & dosage)
• Angiotensin-Converting Enzyme 2 (immunology, metabolism)
• Animals
• Antibodies, Neutralizing (immunology)
• Antibodies, Viral (immunology)
• Antibody Formation (immunology)
• COVID-19 (immunology, prevention & control)
• COVID-19 Vaccines (administration & dosage, immunology)
• Disease Models, Animal
• Heterocyclic Compounds, 3-Ring (administration & dosage, immunology)
• Humans
• Macaca mulatta
• Mice
• Protein Binding
• SARS-CoV-2 (isolation & purification)
• Spike Glycoprotein, Coronavirus (immunology)
• Stearic Acids (administration & dosage, immunology)