• Wen-Hsiang Chen, Xinrong Tao, Anurodh Shankar Agrawal, Abdullah Algaissi, Bi-Hung Peng, Jeroen Pollet, Ulrich Strych, Maria Elena Bottazzi, Peter J Hotez, Sara Lustigman, Lanying Du, Shibo Jiang, and Tseng Chien-Te K CK Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX, USA. Electronic address: sktseng@utmb.edu..
• Texas Children's Hospital Center for Vaccine Development, Houston, TX, USA; Departments of Pediatrics and Molecular Virology & Microbiology, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA.
• Vaccine. 2020 Nov 3; 38 (47): 7533-7541.

AbstractWe developed a severe acute respiratory syndrome (SARS) subunit recombinant protein vaccine candidate based on a high-yielding, yeast-engineered, receptor-binding domain (RBD219-N1) of the SARS beta-coronavirus (SARS-CoV) spike (S) protein. When formulated with Alhydrogel®, RBD219-N1 induced high levels of neutralizing antibodies against both pseudotyped virus and a clinical (mouse-adapted) isolate of SARS-CoV. Here, we report that mice immunized with RBD219-N1/Alhydrogel® were fully protected from lethal SARS-CoV challenge (0% mortality), compared to ~30% mortality in mice immunized with the SARS S protein formulated with Alhydrogel®, and 100% mortality in negative controls. An RBD219-N1 formulation with Alhydrogel® was also superior to the S protein, unadjuvanted RBD, and AddaVax (MF59-like adjuvant)-formulated RBD in inducing specific antibodies and preventing cellular infiltrates in the lungs upon SARS-CoV challenge. Specifically, a formulation with a 1:25 ratio of RBD219-N1 to Alhydrogel® provided high neutralizing antibody titers, 100% protection with non-detectable viral loads with minimal or no eosinophilic pulmonary infiltrates. As a result, this vaccine formulation is under consideration for further development against SARS-CoV and potentially other emerging and re-emerging beta-CoVs such as SARS-CoV-2.Copyright © 2020 Elsevier Ltd. All rights reserved.

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