Development of a two-component recombinant vaccine for COVID-19
IntroductionThough 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 region...
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1514226/full |
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| author | Yi-Sheng Sun Fang Xu Han-Ping Zhu Yong Xia Qiao-Min Li Yuan-Yuan Luo Hang-Jing Lu Bei-Bei Wu Zhen Wang Ping-Ping Yao Zhan Zhou Zhan Zhou |
| author_facet | Yi-Sheng Sun Fang Xu Han-Ping Zhu Yong Xia Qiao-Min Li Yuan-Yuan Luo Hang-Jing Lu Bei-Bei Wu Zhen Wang Ping-Ping Yao Zhan Zhou Zhan Zhou |
| author_sort | Yi-Sheng Sun |
| collection | DOAJ |
| description | IntroductionThough 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.MethodsIn 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.ResultsWe 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.ConclusionThis novel two-component recombinant vaccine exhibits high immunogenicity and offers a potential booster strategy for COVID-19 vaccine development. |
| format | Article |
| id | doaj-art-59a73e6b9f3b4432abc0a3df18afc942 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-59a73e6b9f3b4432abc0a3df18afc9422024-12-20T06:29:13ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-12-011510.3389/fimmu.2024.15142261514226Development of a two-component recombinant vaccine for COVID-19Yi-Sheng Sun0Fang Xu1Han-Ping Zhu2Yong Xia3Qiao-Min Li4Yuan-Yuan Luo5Hang-Jing Lu6Bei-Bei Wu7Zhen Wang8Ping-Ping Yao9Zhan Zhou10Zhan Zhou11Zhejiang Key Lab of Vaccine, Infectious Disease Prevention and Control, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, ChinaZhejiang Key Lab of Vaccine, Infectious Disease Prevention and Control, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, ChinaZhejiang Key Lab of Vaccine, Infectious Disease Prevention and Control, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, ChinaZhejiang Key Lab of Vaccine, Infectious Disease Prevention and Control, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, ChinaInnovation Institute for Artificial Intelligence in Medicine and Zhejiang Provincial Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, ChinaInnovation Institute for Artificial Intelligence in Medicine and Zhejiang Provincial Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, ChinaZhejiang Key Lab of Vaccine, Infectious Disease Prevention and Control, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, ChinaZhejiang Key Lab of Vaccine, Infectious Disease Prevention and Control, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, ChinaZhejiang Key Lab of Vaccine, Infectious Disease Prevention and Control, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, ChinaZhejiang Key Lab of Vaccine, Infectious Disease Prevention and Control, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, ChinaInnovation Institute for Artificial Intelligence in Medicine and Zhejiang Provincial Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, ChinaThe Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, ChinaIntroductionThough 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.MethodsIn 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.ResultsWe 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.ConclusionThis novel two-component recombinant vaccine exhibits high immunogenicity and offers a potential booster strategy for COVID-19 vaccine development.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1514226/fullCOVID-19vaccinereceptor-binding domain (RBD)N-terminal domain (NTD)Fc fusion |
| spellingShingle | Yi-Sheng Sun Fang Xu Han-Ping Zhu Yong Xia Qiao-Min Li Yuan-Yuan Luo Hang-Jing Lu Bei-Bei Wu Zhen Wang Ping-Ping Yao Zhan Zhou Zhan Zhou Development of a two-component recombinant vaccine for COVID-19 Frontiers in Immunology COVID-19 vaccine receptor-binding domain (RBD) N-terminal domain (NTD) Fc fusion |
| title | Development of a two-component recombinant vaccine for COVID-19 |
| title_full | Development of a two-component recombinant vaccine for COVID-19 |
| title_fullStr | Development of a two-component recombinant vaccine for COVID-19 |
| title_full_unstemmed | Development of a two-component recombinant vaccine for COVID-19 |
| title_short | Development of a two-component recombinant vaccine for COVID-19 |
| title_sort | development of a two component recombinant vaccine for covid 19 |
| topic | COVID-19 vaccine receptor-binding domain (RBD) N-terminal domain (NTD) Fc fusion |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1514226/full |
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