RT Journal Article SR Electronic T1 Yeast-Expressed SARS-CoV Recombinant Receptor-Binding Domain (RBD219-N1) Formulated with Aluminum Hydroxide Induces Protective Immunity and Reduces Immune Enhancement JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.05.15.098079 DO 10.1101/2020.05.15.098079 A1 Wen-Hsiang Chen A1 Xinrong Tao A1 Anurodh Agrawal A1 Abdullah Algaissi A1 Bi-Hung Peng A1 Jeroen Pollet A1 Ulrich Strych A1 Maria Elena Bottazzi A1 Peter J. Hotez A1 Sara Lustigman A1 Lanying Du A1 Shibo Jiang A1 Chien-Te K. Tseng YR 2020 UL http://biorxiv.org/content/early/2020/07/05/2020.05.15.098079.abstract AB We 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-level 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 when immunized with the SARS S protein formulated with Alhydrogel®, and 100% mortality in negative controls. An RBD219-N1 formulation 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.Competing Interest StatementThe authors have declared no competing interest.