Elsevier

Vaccine

Volume 38, Issue 47, 3 November 2020, Pages 7533-7541
Vaccine

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

https://doi.org/10.1016/j.vaccine.2020.09.061Get rights and content

Highlights

  • 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.

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.

Keywords

Coronavirus
Vaccine
Eosinophil infiltration
Severe acute respiratory syndrome
Recombinant protein

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1

These authors contributed to the manuscript equally.

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