tetano
Editor, Senior Moderator
Front Immunol
. 2024 Dec 20:15:1514226.
doi: 10.3389/fimmu.2024.1514226. eCollection 2024. Development of a two-component recombinant vaccine for COVID-19
Yi-Sheng Sun[SUP] 1 [/SUP], Fang Xu[SUP] 1 [/SUP], Han-Ping Zhu[SUP] 1 [/SUP], Yong Xia[SUP] 1 [/SUP], Qiao-Min Li[SUP] 2 [/SUP], Yuan-Yuan Luo[SUP] 2 [/SUP], Hang-Jing Lu[SUP] 1 [/SUP], Bei-Bei Wu[SUP] 1 [/SUP], Zhen Wang[SUP] 1 [/SUP], Ping-Ping Yao[SUP] 1 [/SUP], Zhan Zhou[SUP] 2 3 [/SUP]
Affiliations
Introduction: Though COVID-19 as a public health emergency of international concern (PHEIC) was declared to be ended by the WHO, it continues to pose a significant threat to human society. Vaccination remains one of the most effective methods for preventing COVID-19. While most of the antigenic regions are found in the receptor binding domain (RBD), the N-terminal domain (NTD) of the S protein is another crucial region for inducing neutralizing antibodies (nAbs) against COVID-19.
Methods: In the two-dose immunization experiment, female BALB/c mice were intramuscularly immunized with different ratios of RBD-Fc and NTD-Fc proteins, with a total protein dose of 8 μg per mouse. Mice were immunized on day 0 and boosted on day 7. In the sequential immunization experiment, groups of female BALB/c mice were immunized with two doses of the inactivated SARS-CoV-2 vaccine (prototype strain) on day 0 and 7. On day 28, mice were boosted with RBD-Fc, NTD-Fc, RBD-Fc/NTD-Fc (9:1), RBD-Fc/NTD-Fc (3:1), inactivated SARS-CoV-2 vaccine (protoype strain), inactivated SARS-CoV-2 vaccine (omicron strain), individually. The IgG antibodies were detected using ELISA, while the neutralizing antibodies were measured through a microneutralization assay utilizing both the prototype and omicron strains. The ELISPOT assays were performed to measure the secretion of IL-4 and IFN-γ, and the concentrations of secreted IL-2 and IL-10 in the supernatants were measured by ELISA.
Results: We have first developed a two-component recombinant vaccine for COVID-19 based on RBD-Fc and NTD-Fc proteins, with an optimal RBD-Fc/NTD-Fc ratio of 3:1. This novel two-component vaccine demonstrated the ability to induce durable and potent IgG antibodies, as well as the neutralizing antibodies in both the two-dose homologous and sequential vaccinations. Heterologous booster with this two-component vaccine could induce higher neutralizing antibody titers than the homologous group. Additionally, the vaccine elicited relatively balanced Th1- and Th2-cell immune responses.
Conclusion: This novel two-component recombinant vaccine exhibits high immunogenicity and offers a potential booster strategy for COVID-19 vaccine development.
Keywords: COVID-19; Fc fusion; N-terminal domain (NTD); receptor-binding domain (RBD); vaccine.
. 2024 Dec 20:15:1514226.
doi: 10.3389/fimmu.2024.1514226. eCollection 2024. Development of a two-component recombinant vaccine for COVID-19
Yi-Sheng Sun[SUP] 1 [/SUP], Fang Xu[SUP] 1 [/SUP], Han-Ping Zhu[SUP] 1 [/SUP], Yong Xia[SUP] 1 [/SUP], Qiao-Min Li[SUP] 2 [/SUP], Yuan-Yuan Luo[SUP] 2 [/SUP], Hang-Jing Lu[SUP] 1 [/SUP], Bei-Bei Wu[SUP] 1 [/SUP], Zhen Wang[SUP] 1 [/SUP], Ping-Ping Yao[SUP] 1 [/SUP], Zhan Zhou[SUP] 2 3 [/SUP]
Affiliations
- PMID: 39759508
- PMCID: PMC11695372
- DOI: 10.3389/fimmu.2024.1514226
Introduction: Though COVID-19 as a public health emergency of international concern (PHEIC) was declared to be ended by the WHO, it continues to pose a significant threat to human society. Vaccination remains one of the most effective methods for preventing COVID-19. While most of the antigenic regions are found in the receptor binding domain (RBD), the N-terminal domain (NTD) of the S protein is another crucial region for inducing neutralizing antibodies (nAbs) against COVID-19.
Methods: In the two-dose immunization experiment, female BALB/c mice were intramuscularly immunized with different ratios of RBD-Fc and NTD-Fc proteins, with a total protein dose of 8 μg per mouse. Mice were immunized on day 0 and boosted on day 7. In the sequential immunization experiment, groups of female BALB/c mice were immunized with two doses of the inactivated SARS-CoV-2 vaccine (prototype strain) on day 0 and 7. On day 28, mice were boosted with RBD-Fc, NTD-Fc, RBD-Fc/NTD-Fc (9:1), RBD-Fc/NTD-Fc (3:1), inactivated SARS-CoV-2 vaccine (protoype strain), inactivated SARS-CoV-2 vaccine (omicron strain), individually. The IgG antibodies were detected using ELISA, while the neutralizing antibodies were measured through a microneutralization assay utilizing both the prototype and omicron strains. The ELISPOT assays were performed to measure the secretion of IL-4 and IFN-γ, and the concentrations of secreted IL-2 and IL-10 in the supernatants were measured by ELISA.
Results: We have first developed a two-component recombinant vaccine for COVID-19 based on RBD-Fc and NTD-Fc proteins, with an optimal RBD-Fc/NTD-Fc ratio of 3:1. This novel two-component vaccine demonstrated the ability to induce durable and potent IgG antibodies, as well as the neutralizing antibodies in both the two-dose homologous and sequential vaccinations. Heterologous booster with this two-component vaccine could induce higher neutralizing antibody titers than the homologous group. Additionally, the vaccine elicited relatively balanced Th1- and Th2-cell immune responses.
Conclusion: This novel two-component recombinant vaccine exhibits high immunogenicity and offers a potential booster strategy for COVID-19 vaccine development.
Keywords: COVID-19; Fc fusion; N-terminal domain (NTD); receptor-binding domain (RBD); vaccine.