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

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, Chien Te K. Tseng

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)7533-7541
Number of pages9
JournalVaccine
Volume38
Issue number47
DOIs
StatePublished - Nov 3 2020

Keywords

  • Coronavirus
  • Eosinophil infiltration
  • Recombinant protein
  • Severe acute respiratory syndrome
  • Vaccine

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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