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Inactivated SARS-CoV-2 Vaccine Shows Cross-Protection against Bat SARS-Related Coronaviruses in Human ACE2 Transgenic Mice.
J Virol. 2022 04 27; 96(8):e0016922.JV

Abstract

Severe acute respiratory syndrome coronavirus (SARS-CoV-1) and SARS-CoV-2 are highly pathogenic to humans and have caused pandemics in 2003 and 2019, respectively. Genetically diverse SARS-related coronaviruses (SARSr-CoVs) have been detected or isolated from bats, and some of these viruses have been demonstrated to utilize human angiotensin-converting enzyme 2 (ACE2) as a receptor and to have the potential to spill over to humans. A pan-sarbecovirus vaccine that provides protection against SARSr-CoV infection is urgently needed. In this study, we evaluated the protective efficacy of an inactivated SARS-CoV-2 vaccine against recombinant SARSr-CoVs carrying two different spike proteins (named rWIV1 and rRsSHC014S, respectively). Although serum neutralizing assays showed limited cross-reactivity between the three viruses, the inactivated SARS-CoV-2 vaccine provided full protection against SARS-CoV-2 and rWIV1 and partial protection against rRsSHC014S infection in human ACE2 transgenic mice. Passive transfer of SARS-CoV-2-vaccinated mouse sera provided low protection for rWIV1 but not for rRsSHC014S infection in human ACE2 mice. A specific cellular immune response induced by WIV1 membrane protein peptides was detected in the vaccinated animals, which may explain the cross-protection of the inactivated vaccine. This study shows the possibility of developing a pan-sarbecovirus vaccine against SARSr-CoVs for future preparedness. IMPORTANCE The genetic diversity of SARSr-CoVs in wildlife and their potential risk of cross-species infection highlight the necessity of developing wide-spectrum vaccines against infection of various SARSr-CoVs. In this study, we tested the protective efficacy of the SARS-CoV-2 inactivated vaccine (IAV) against two SARSr-CoVs with different spike proteins in human ACE2 transgenic mice. We demonstrate that the SARS-CoV-2 IAV provides full protection against rWIV1 and partial protection against rRsSHC014S. The T-cell response stimulated by the M protein may account for the cross protection against heterogeneous SARSr-CoVs. Our findings suggest the feasibility of the development of pan-sarbecovirus vaccines, which can be a strategy of preparedness for future outbreaks caused by novel SARSr-CoVs from wildlife.

Authors+Show Affiliations

Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. University of Chinese Academy of Sciences, Beijing, China.Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. University of Chinese Academy of Sciences, Beijing, China.Wuhan Institute of Biological Products Co. Ltd., Jiangxia District, Wuhan, China.Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. University of Chinese Academy of Sciences, Beijing, China.Wuhan Institute of Biological Products Co. Ltd., Jiangxia District, Wuhan, China.Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. University of Chinese Academy of Sciences, Beijing, China.Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. University of Chinese Academy of Sciences, Beijing, China.Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. University of Chinese Academy of Sciences, Beijing, China.Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.Wuhan Institute of Biological Products Co. Ltd., Jiangxia District, Wuhan, China.Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

35343762

Citation

Liu, Mei-Qin, et al. "Inactivated SARS-CoV-2 Vaccine Shows Cross-Protection Against Bat SARS-Related Coronaviruses in Human ACE2 Transgenic Mice." Journal of Virology, vol. 96, no. 8, 2022, pp. e0016922.
Liu MQ, Jiang RD, Guo J, et al. Inactivated SARS-CoV-2 Vaccine Shows Cross-Protection against Bat SARS-Related Coronaviruses in Human ACE2 Transgenic Mice. J Virol. 2022;96(8):e0016922.
Liu, M. Q., Jiang, R. D., Guo, J., Chen, Y., Yang, D. S., Wang, X., Lin, H. F., Li, A., Li, B., Hu, B., Wang, Z. J., Yang, X. L., & Shi, Z. L. (2022). Inactivated SARS-CoV-2 Vaccine Shows Cross-Protection against Bat SARS-Related Coronaviruses in Human ACE2 Transgenic Mice. Journal of Virology, 96(8), e0016922. https://doi.org/10.1128/jvi.00169-22
Liu MQ, et al. Inactivated SARS-CoV-2 Vaccine Shows Cross-Protection Against Bat SARS-Related Coronaviruses in Human ACE2 Transgenic Mice. J Virol. 2022 04 27;96(8):e0016922. PubMed PMID: 35343762.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inactivated SARS-CoV-2 Vaccine Shows Cross-Protection against Bat SARS-Related Coronaviruses in Human ACE2 Transgenic Mice. AU - Liu,Mei-Qin, AU - Jiang,Ren-Di, AU - Guo,Jing, AU - Chen,Ying, AU - Yang,Dong-Sheng, AU - Wang,Xi, AU - Lin,Hao-Feng, AU - Li,Ang, AU - Li,Bei, AU - Hu,Ben, AU - Wang,Ze-Jun, AU - Yang,Xing-Lou, AU - Shi,Zheng-Li, Y1 - 2022/03/28/ PY - 2022/3/29/pubmed PY - 2022/4/30/medline PY - 2022/3/28/entrez KW - SARS-CoV-2 KW - bat SARS-related coronavirus KW - cross-protection KW - inactivated vaccine SP - e0016922 EP - e0016922 JF - Journal of virology JO - J Virol VL - 96 IS - 8 N2 - Severe acute respiratory syndrome coronavirus (SARS-CoV-1) and SARS-CoV-2 are highly pathogenic to humans and have caused pandemics in 2003 and 2019, respectively. Genetically diverse SARS-related coronaviruses (SARSr-CoVs) have been detected or isolated from bats, and some of these viruses have been demonstrated to utilize human angiotensin-converting enzyme 2 (ACE2) as a receptor and to have the potential to spill over to humans. A pan-sarbecovirus vaccine that provides protection against SARSr-CoV infection is urgently needed. In this study, we evaluated the protective efficacy of an inactivated SARS-CoV-2 vaccine against recombinant SARSr-CoVs carrying two different spike proteins (named rWIV1 and rRsSHC014S, respectively). Although serum neutralizing assays showed limited cross-reactivity between the three viruses, the inactivated SARS-CoV-2 vaccine provided full protection against SARS-CoV-2 and rWIV1 and partial protection against rRsSHC014S infection in human ACE2 transgenic mice. Passive transfer of SARS-CoV-2-vaccinated mouse sera provided low protection for rWIV1 but not for rRsSHC014S infection in human ACE2 mice. A specific cellular immune response induced by WIV1 membrane protein peptides was detected in the vaccinated animals, which may explain the cross-protection of the inactivated vaccine. This study shows the possibility of developing a pan-sarbecovirus vaccine against SARSr-CoVs for future preparedness. IMPORTANCE The genetic diversity of SARSr-CoVs in wildlife and their potential risk of cross-species infection highlight the necessity of developing wide-spectrum vaccines against infection of various SARSr-CoVs. In this study, we tested the protective efficacy of the SARS-CoV-2 inactivated vaccine (IAV) against two SARSr-CoVs with different spike proteins in human ACE2 transgenic mice. We demonstrate that the SARS-CoV-2 IAV provides full protection against rWIV1 and partial protection against rRsSHC014S. The T-cell response stimulated by the M protein may account for the cross protection against heterogeneous SARSr-CoVs. Our findings suggest the feasibility of the development of pan-sarbecovirus vaccines, which can be a strategy of preparedness for future outbreaks caused by novel SARSr-CoVs from wildlife. SN - 1098-5514 UR - https://www.unboundmedicine.com/medline/citation/35343762/Inactivated_SARS_CoV_2_Vaccine_Shows_Cross_Protection_against_Bat_SARS_Related_Coronaviruses_in_Human_ACE2_Transgenic_Mice_ L2 - https://journals.asm.org/doi/10.1128/jvi.00169-22?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -