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Yeast-expressed SARS-CoV recombinant receptor-binding domain (RBD219-N1) formulated with aluminum hydroxide induces protective immunity and reduces immune enhancement.
- Source :
-
Vaccine . Nov2020, Vol. 38 Issue 47, p7533-7541. 9p. - Publication Year :
- 2020
-
Abstract
- • 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0264410X
- Volume :
- 38
- Issue :
- 47
- Database :
- Academic Search Index
- Journal :
- Vaccine
- Publication Type :
- Academic Journal
- Accession number :
- 146633457
- Full Text :
- https://doi.org/10.1016/j.vaccine.2020.09.061