tetano
Editor, Senior Moderator
J Virol
. 2022 Mar 28;e0016922.
doi: 10.1128/jvi.00169-22. Online ahead of print.
Inactivated SARS-CoV-2 Vaccine Shows Cross-Protection against Bat SARS-Related Coronaviruses in Human ACE2 Transgenic Mice
Mei-Qin Liu[SUP] #[/SUP][SUP] 1 2 [/SUP], Ren-Di Jiang[SUP] #[/SUP][SUP] 1 2 [/SUP], Jing Guo[SUP] #[/SUP][SUP] 3 [/SUP], Ying Chen[SUP] #[/SUP][SUP] 1 2 [/SUP], Dong-Sheng Yang[SUP] 3 [/SUP], Xi Wang[SUP] 1 2 [/SUP], Hao-Feng Lin[SUP] 1 2 [/SUP], Ang Li[SUP] 1 2 [/SUP], Bei Li[SUP] 1 [/SUP], Ben Hu[SUP] 1 [/SUP], Ze-Jun Wang[SUP] 3 [/SUP], Xing-Lou Yang[SUP] 1 [/SUP], Zheng-Li Shi[SUP] 1 [/SUP]
Affiliations
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.
Keywords: SARS-CoV-2; bat SARS-related coronavirus; cross-protection; inactivated vaccine.
. 2022 Mar 28;e0016922.
doi: 10.1128/jvi.00169-22. Online ahead of print.
Inactivated SARS-CoV-2 Vaccine Shows Cross-Protection against Bat SARS-Related Coronaviruses in Human ACE2 Transgenic Mice
Mei-Qin Liu[SUP] #[/SUP][SUP] 1 2 [/SUP], Ren-Di Jiang[SUP] #[/SUP][SUP] 1 2 [/SUP], Jing Guo[SUP] #[/SUP][SUP] 3 [/SUP], Ying Chen[SUP] #[/SUP][SUP] 1 2 [/SUP], Dong-Sheng Yang[SUP] 3 [/SUP], Xi Wang[SUP] 1 2 [/SUP], Hao-Feng Lin[SUP] 1 2 [/SUP], Ang Li[SUP] 1 2 [/SUP], Bei Li[SUP] 1 [/SUP], Ben Hu[SUP] 1 [/SUP], Ze-Jun Wang[SUP] 3 [/SUP], Xing-Lou Yang[SUP] 1 [/SUP], Zheng-Li Shi[SUP] 1 [/SUP]
Affiliations
- PMID: 35343762
- DOI: 10.1128/jvi.00169-22
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.
Keywords: SARS-CoV-2; bat SARS-related coronavirus; cross-protection; inactivated vaccine.