Trivalent recombinant protein vaccine induces cross-neutralization against XBB lineage and JN.1 subvariants: preclinical and phase 1 clinical trials
Abstract The immune escape capacities of XBB variants necessitate the authorization of vaccines with these antigens. In this study, we produce three recombinant trimeric proteins from the RBD sequences of Delta, BA.5, and XBB.1.5, formulating a trivalent vaccine (Tri-Vac) with an MF59-like adjuvant...
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Nature Portfolio
2024-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55087-z |
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| author | Jingyun Yang Weiqi Hong Huashan Shi Cai He Hong Lei Yanan Zhou Hao Yang Aqu Alu Zimin Chen Yun Yang Wenhai Yu Cong Tang Junbin Wang Bai Li Qing Huang Jiong Li Li Yang Wei Wang Guobo Shen Jinliang Yang Zhiwei Zhao Xiangrong Song Zhaoming Su Yuquan Wei Qiangming Sun Shuaiyao Lu Zhenling Wang Youchun Wang Guangwen Lu Weimin Li Xiawei Wei |
| author_facet | Jingyun Yang Weiqi Hong Huashan Shi Cai He Hong Lei Yanan Zhou Hao Yang Aqu Alu Zimin Chen Yun Yang Wenhai Yu Cong Tang Junbin Wang Bai Li Qing Huang Jiong Li Li Yang Wei Wang Guobo Shen Jinliang Yang Zhiwei Zhao Xiangrong Song Zhaoming Su Yuquan Wei Qiangming Sun Shuaiyao Lu Zhenling Wang Youchun Wang Guangwen Lu Weimin Li Xiawei Wei |
| author_sort | Jingyun Yang |
| collection | DOAJ |
| description | Abstract The immune escape capacities of XBB variants necessitate the authorization of vaccines with these antigens. In this study, we produce three recombinant trimeric proteins from the RBD sequences of Delta, BA.5, and XBB.1.5, formulating a trivalent vaccine (Tri-Vac) with an MF59-like adjuvant at a 1:1:4 ratio. Tri-Vac demonstrates immunogenicity in female NIH mice, inducing cross-neutralization against various SARS-CoV-2 variants, including pre-Omicron and Omicron BA.2.75, BA.5, and XBB lineages. It elicits measurable antigen-specific T cell responses, germinal center B cell responses, and T follicular helper responses, effectively protecting against live Omicron XBB.1.16 challenges. Protective immunity is maintained long-term, with sustained neutralizing antibodies and T cell responses, as well as memory B cells and long-lived plasma cells observed by day 210 post-immunization. Tri-Vac also serves as a candidate booster for enhancing immunity after three doses of inactivated virus or mRNA vaccines. A phase 1 investigator-initiated trial was initiated to assess safety and immunogenicity in humans, focusing on the primary endpoint of adverse reactions within 7 days and key secondary endpoints including the geometric mean titers (GMTs) of serum neutralizing antibodies within 30 days and 6 months post-vaccination, as well as adverse events within 30 days and serious adverse events within 6 months post-vaccination. Preliminary data indicate Tri-Vac has good safety and immunogenicity, improving neutralization against multiple variants, including JN.1, in previously vaccinated individuals, highlighting its clinical potential for protecting against SARS-CoV-2 variants. The registration number of this clinical trial is ChiCTR2200067245. |
| format | Article |
| id | doaj-art-4a9cdd295fb04507a4b5e413115fc72b |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
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| series | Nature Communications |
| spelling | doaj-art-4a9cdd295fb04507a4b5e413115fc72b2025-01-05T12:34:37ZengNature PortfolioNature Communications2041-17232024-12-0115111810.1038/s41467-024-55087-zTrivalent recombinant protein vaccine induces cross-neutralization against XBB lineage and JN.1 subvariants: preclinical and phase 1 clinical trialsJingyun Yang0Weiqi Hong1Huashan Shi2Cai He3Hong Lei4Yanan Zhou5Hao Yang6Aqu Alu7Zimin Chen8Yun Yang9Wenhai Yu10Cong Tang11Junbin Wang12Bai Li13Qing Huang14Jiong Li15Li Yang16Wei Wang17Guobo Shen18Jinliang Yang19Zhiwei Zhao20Xiangrong Song21Zhaoming Su22Yuquan Wei23Qiangming Sun24Shuaiyao Lu25Zhenling Wang26Youchun Wang27Guangwen Lu28Weimin Li29Xiawei Wei30Laboratory of Aging Research and Cancer Drug Target, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityNational Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeNational Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeLaboratory of Aging Research and Cancer Drug Target, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityNational Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeNational Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeNational Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeNational Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeNational Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeNational Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeLaboratory of Aging Research and Cancer Drug Target, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityNational Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeNational Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeLaboratory of Aging Research and Cancer Drug Target, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityNational Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeLaboratory of Aging Research and Cancer Drug Target, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityDepartment of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityAbstract The immune escape capacities of XBB variants necessitate the authorization of vaccines with these antigens. In this study, we produce three recombinant trimeric proteins from the RBD sequences of Delta, BA.5, and XBB.1.5, formulating a trivalent vaccine (Tri-Vac) with an MF59-like adjuvant at a 1:1:4 ratio. Tri-Vac demonstrates immunogenicity in female NIH mice, inducing cross-neutralization against various SARS-CoV-2 variants, including pre-Omicron and Omicron BA.2.75, BA.5, and XBB lineages. It elicits measurable antigen-specific T cell responses, germinal center B cell responses, and T follicular helper responses, effectively protecting against live Omicron XBB.1.16 challenges. Protective immunity is maintained long-term, with sustained neutralizing antibodies and T cell responses, as well as memory B cells and long-lived plasma cells observed by day 210 post-immunization. Tri-Vac also serves as a candidate booster for enhancing immunity after three doses of inactivated virus or mRNA vaccines. A phase 1 investigator-initiated trial was initiated to assess safety and immunogenicity in humans, focusing on the primary endpoint of adverse reactions within 7 days and key secondary endpoints including the geometric mean titers (GMTs) of serum neutralizing antibodies within 30 days and 6 months post-vaccination, as well as adverse events within 30 days and serious adverse events within 6 months post-vaccination. Preliminary data indicate Tri-Vac has good safety and immunogenicity, improving neutralization against multiple variants, including JN.1, in previously vaccinated individuals, highlighting its clinical potential for protecting against SARS-CoV-2 variants. The registration number of this clinical trial is ChiCTR2200067245.https://doi.org/10.1038/s41467-024-55087-z |
| spellingShingle | Jingyun Yang Weiqi Hong Huashan Shi Cai He Hong Lei Yanan Zhou Hao Yang Aqu Alu Zimin Chen Yun Yang Wenhai Yu Cong Tang Junbin Wang Bai Li Qing Huang Jiong Li Li Yang Wei Wang Guobo Shen Jinliang Yang Zhiwei Zhao Xiangrong Song Zhaoming Su Yuquan Wei Qiangming Sun Shuaiyao Lu Zhenling Wang Youchun Wang Guangwen Lu Weimin Li Xiawei Wei Trivalent recombinant protein vaccine induces cross-neutralization against XBB lineage and JN.1 subvariants: preclinical and phase 1 clinical trials Nature Communications |
| title | Trivalent recombinant protein vaccine induces cross-neutralization against XBB lineage and JN.1 subvariants: preclinical and phase 1 clinical trials |
| title_full | Trivalent recombinant protein vaccine induces cross-neutralization against XBB lineage and JN.1 subvariants: preclinical and phase 1 clinical trials |
| title_fullStr | Trivalent recombinant protein vaccine induces cross-neutralization against XBB lineage and JN.1 subvariants: preclinical and phase 1 clinical trials |
| title_full_unstemmed | Trivalent recombinant protein vaccine induces cross-neutralization against XBB lineage and JN.1 subvariants: preclinical and phase 1 clinical trials |
| title_short | Trivalent recombinant protein vaccine induces cross-neutralization against XBB lineage and JN.1 subvariants: preclinical and phase 1 clinical trials |
| title_sort | trivalent recombinant protein vaccine induces cross neutralization against xbb lineage and jn 1 subvariants preclinical and phase 1 clinical trials |
| url | https://doi.org/10.1038/s41467-024-55087-z |
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