tetano
Editor, Senior Moderator
Vaccine
. 2020 Sep 22;S0264-410X(20)31232-9.
doi: 10.1016/j.vaccine.2020.09.061. Online ahead of print.
Yeast-expressed SARS-CoV recombinant receptor-binding domain (RBD219-N1) formulated with aluminum hydroxide induces protective immunity and reduces immune enhancement
Wen-Hsiang Chen[SUP] 1 [/SUP], Xinrong Tao[SUP] 2 [/SUP], Anurodh Shankar Agrawal[SUP] 3 [/SUP], Abdullah Algaissi[SUP] 4 [/SUP], Bi-Hung Peng[SUP] 5 [/SUP], Jeroen Pollet[SUP] 1 [/SUP], Ulrich Strych[SUP] 1 [/SUP], Maria Elena Bottazzi[SUP] 6 [/SUP], Peter J Hotez[SUP] 7 [/SUP], Sara Lustigman[SUP] 8 [/SUP], Lanying Du[SUP] 8 [/SUP], Shibo Jiang[SUP] 8 [/SUP], Chien-Te K Tseng[SUP] 9 [/SUP]
Affiliations
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; Eosinophil infiltration; Recombinant protein; Severe acute respiratory syndrome; Vaccine.
. 2020 Sep 22;S0264-410X(20)31232-9.
doi: 10.1016/j.vaccine.2020.09.061. Online ahead of print.
Yeast-expressed SARS-CoV recombinant receptor-binding domain (RBD219-N1) formulated with aluminum hydroxide induces protective immunity and reduces immune enhancement
Wen-Hsiang Chen[SUP] 1 [/SUP], Xinrong Tao[SUP] 2 [/SUP], Anurodh Shankar Agrawal[SUP] 3 [/SUP], Abdullah Algaissi[SUP] 4 [/SUP], Bi-Hung Peng[SUP] 5 [/SUP], Jeroen Pollet[SUP] 1 [/SUP], Ulrich Strych[SUP] 1 [/SUP], Maria Elena Bottazzi[SUP] 6 [/SUP], Peter J Hotez[SUP] 7 [/SUP], Sara Lustigman[SUP] 8 [/SUP], Lanying Du[SUP] 8 [/SUP], Shibo Jiang[SUP] 8 [/SUP], Chien-Te K Tseng[SUP] 9 [/SUP]
Affiliations
- PMID: 33039209
- PMCID: PMC7508514
- DOI: 10.1016/j.vaccine.2020.09.061
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; Eosinophil infiltration; Recombinant protein; Severe acute respiratory syndrome; Vaccine.