Yeast-expressed SARS-CoV recombinant receptor-binding domain (RBD219-N1) formulated with aluminum hydroxide induces protective immunity and reduces immune enhancement

• Published in: Vaccine Vol. 38; no. 47; pp. 7533 - 7541
• Main Authors: Chen, Wen-Hsiang, Tao, Xinrong, Agrawal, Anurodh Shankar, Algaissi, Abdullah, Peng, Bi-Hung, Pollet, Jeroen, Strych, Ulrich, Bottazzi, Maria Elena, Hotez, Peter J., Lustigman, Sara, Du, Lanying, Jiang, Shibo, Tseng, Chien-Te K.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 03-11-2020; Elsevier Limited
• Subjects: Aluminum; Aluminum hydroxide; Aluminum Hydroxide - administration & dosage; Animals; Antibodies; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; Antigens; Betacoronavirus - immunology; Binding; Chromatography; Coronavirus; Coronavirus Infections - immunology; Coronavirus Infections - prevention & control; Coronaviruses; COVID-19; COVID-19 Vaccines; Domains; Eosinophil infiltration; Epidemics; Fatalities; Female; Glycerol; Histopathology; Humans; Immunity; Immunity (Disease); Immunization; Leukocytes (eosinophilic); Mice; Mice, Inbred BALB C; Mortality; Neutralizing; Pandemics; Pandemics - prevention & control; Pneumonia, Viral - prevention & control; Protein Domains - immunology; Proteins; Receptors; Recombinant protein; Recombinant Proteins - immunology; Respiratory diseases; SARS-CoV-2; Severe acute respiratory syndrome; Severe Acute Respiratory Syndrome - prevention & control; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - immunology; Vaccine; Vaccines; Vaccines, Subunit - immunology; Vaccines, Synthetic - immunology; Viral diseases; Viral Load - immunology; Viral Vaccines - immunology; Viruses; Yeast; Yeasts; United States > US; Vaccine; Coronavirus; Recombinant protein; Severe acute respiratory syndrome; Eosinophil infiltration
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2020.09.061

•A SARS-CoV RBD vaccine on alum provides high neutralizing titers and 100% survival.•A SARS-CoV RBD vaccine on alum prevents pulmonary cellular infiltrates upon virus challenge.•A SARS-CoV RBD vaccine on alum greatly reduces lung eosinophils compared to a vaccine comprised of the SARS-CoV S protein.•The SARS-CoV RBD vaccine on alum is being developed as a human vaccine.
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 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.