tetano
Editor, Senior Moderator
Mol Immunol
. 2022 Jun 23;149:107-118.
doi: 10.1016/j.molimm.2022.06.007. Online ahead of print.
Preclinical study of formulated recombinant nucleocapsid protein, the receptor binding domain of the spike protein, and truncated spike (S1) protein as vaccine candidates against COVID-19 in animal models
Shahram Nazarian[SUP] 1 [/SUP], Gholamreza Olad[SUP] 2 [/SUP], Raziyeh Abdolhamidi[SUP] 3 [/SUP], Mohammad Javad Motamedi[SUP] 4 [/SUP], Rouhollah Kazemi[SUP] 4 [/SUP], Emad Kordbacheh[SUP] 1 [/SUP], Alireza Felagari[SUP] 1 [/SUP], Hanieh Olad[SUP] 5 [/SUP], Ali Ahmadi[SUP] 3 [/SUP], Alireza Bahiraee[SUP] 6 [/SUP], Parisa Farahani[SUP] 3 [/SUP], Leila Haghighi[SUP] 6 [/SUP], Faezeh Hassani[SUP] 6 [/SUP], Vahideh Hajhassan[SUP] 4 [/SUP], Mona Nadi[SUP] 4 [/SUP], Abdolkarim Sheikhi[SUP] 7 [/SUP], Jafar Salimian[SUP] 8 [/SUP], Jafar Amani[SUP] 9 [/SUP]
Affiliations
Abstract
Background: In this pre-clinical study, we designed a candidate vaccine based on severe acute respiratory syndrome-related -coronavirus 2 (SARS-CoV-2) antigens and evaluated its safety and immunogenicity.
Methods: SARS-CoV-2 recombinant protein antigens, including truncated spike protein (SS1, lacking the N-terminal domain of S1), receptor-binding domain (RBD), and nucleoprotein (N) were used. Immunization program was performed via injection of RBD, SS1 +RBD, and SS1 +N along with different adjuvants, Alum, AS03, and Montanide at doses of 0, 40, 80, and 120 μg at three-time points in mice, rabbits, and primates. The humoral and cellular immunity were analyzed by ELISA, VNT, splenocyte cytokine assay, and flow cytometry.
Results: The candidate vaccine produced strong IgG antibody titers at doses of 80 and 120 μg on days 35 and 42. Even though AS03 and Montanide produced high-titer antibodies compared to Alum adjuvant, these sera did not neutralize the virus. Strong virus neutralization was recorded during immunization with SS1 +RBD and RBD with Alum. AS03 and Montanide showed a strong humoral and cellular immunity; however, Alum showed mild to moderate cellular responses. Ultimately, no cytotoxicity and pathologic change were observed.
Conclusion: These findings strongly suggest that RBD with Alum adjuvant is highly immunogenic as a potential vaccine.
Keywords: COVID-19; Immunogenicity; Receptor binding domain; SARS-CoV-2; Subunit vaccine.
. 2022 Jun 23;149:107-118.
doi: 10.1016/j.molimm.2022.06.007. Online ahead of print.
Preclinical study of formulated recombinant nucleocapsid protein, the receptor binding domain of the spike protein, and truncated spike (S1) protein as vaccine candidates against COVID-19 in animal models
Shahram Nazarian[SUP] 1 [/SUP], Gholamreza Olad[SUP] 2 [/SUP], Raziyeh Abdolhamidi[SUP] 3 [/SUP], Mohammad Javad Motamedi[SUP] 4 [/SUP], Rouhollah Kazemi[SUP] 4 [/SUP], Emad Kordbacheh[SUP] 1 [/SUP], Alireza Felagari[SUP] 1 [/SUP], Hanieh Olad[SUP] 5 [/SUP], Ali Ahmadi[SUP] 3 [/SUP], Alireza Bahiraee[SUP] 6 [/SUP], Parisa Farahani[SUP] 3 [/SUP], Leila Haghighi[SUP] 6 [/SUP], Faezeh Hassani[SUP] 6 [/SUP], Vahideh Hajhassan[SUP] 4 [/SUP], Mona Nadi[SUP] 4 [/SUP], Abdolkarim Sheikhi[SUP] 7 [/SUP], Jafar Salimian[SUP] 8 [/SUP], Jafar Amani[SUP] 9 [/SUP]
Affiliations
- PMID: 35802999
- PMCID: PMC9222294
- DOI: 10.1016/j.molimm.2022.06.007
Abstract
Background: In this pre-clinical study, we designed a candidate vaccine based on severe acute respiratory syndrome-related -coronavirus 2 (SARS-CoV-2) antigens and evaluated its safety and immunogenicity.
Methods: SARS-CoV-2 recombinant protein antigens, including truncated spike protein (SS1, lacking the N-terminal domain of S1), receptor-binding domain (RBD), and nucleoprotein (N) were used. Immunization program was performed via injection of RBD, SS1 +RBD, and SS1 +N along with different adjuvants, Alum, AS03, and Montanide at doses of 0, 40, 80, and 120 μg at three-time points in mice, rabbits, and primates. The humoral and cellular immunity were analyzed by ELISA, VNT, splenocyte cytokine assay, and flow cytometry.
Results: The candidate vaccine produced strong IgG antibody titers at doses of 80 and 120 μg on days 35 and 42. Even though AS03 and Montanide produced high-titer antibodies compared to Alum adjuvant, these sera did not neutralize the virus. Strong virus neutralization was recorded during immunization with SS1 +RBD and RBD with Alum. AS03 and Montanide showed a strong humoral and cellular immunity; however, Alum showed mild to moderate cellular responses. Ultimately, no cytotoxicity and pathologic change were observed.
Conclusion: These findings strongly suggest that RBD with Alum adjuvant is highly immunogenic as a potential vaccine.
Keywords: COVID-19; Immunogenicity; Receptor binding domain; SARS-CoV-2; Subunit vaccine.