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
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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