tetano
Editor, Senior Moderator
Front Immunol
. 2025 Mar 28:16:1541269.
doi: 10.3389/fimmu.2025.1541269. eCollection 2025. Anti-S2 antibodies responsible for the SARS-CoV-2 infection-induced serological cross-reactivity against MERS-CoV and MERS-related coronaviruses
Siyuan Sun[SUP] #[/SUP][SUP] 1 [/SUP], Jiaying He[SUP] #[/SUP][SUP] 2 [/SUP], Luotian Liu[SUP] #[/SUP][SUP] 1 [/SUP], Yuzhen Zhu[SUP] #[/SUP][SUP] 3 [/SUP], Qingsong Zhang[SUP] #[/SUP][SUP] 1 [/SUP], Yinong Qiu[SUP] #[/SUP][SUP] 1 [/SUP], Yuru Han[SUP] 1 [/SUP], Song Xue[SUP] 1 [/SUP], Xiaofang Peng[SUP] 1 [/SUP], Yiming Long[SUP] 1 [/SUP], Tianyu Lu[SUP] 1 [/SUP], Wei Wu[SUP] 1 [/SUP], Anqi Xia[SUP] 1 [/SUP], Yunjiao Zhou[SUP] 4 [/SUP], Yan Yan[SUP] 1 [/SUP], Yidan Gao[SUP] 1 [/SUP], Lu Lu[SUP] 1 [/SUP], Lei Sun[SUP] 1 [/SUP], Minxiang Xie[SUP] 1 [/SUP], Qiao Wang[SUP] 1 [/SUP]
Affiliations
Sarbecoviruses, such as SARS-CoV-2, utilize angiotensin-converting enzyme 2 (ACE2) as the entry receptor; while merbecoviruses, such as MERS-CoV, use dipeptidyl peptidase 4 (DPP4) for viral entry. Recently, several MERS-related coronaviruses, NeoCoV and PDF-2180, were reported to use ACE2, the same receptor as SARS-CoV-2, to enter cells, raising the possibility of potential recombination between SARS-CoV-2 and MERS-related coronaviruses within the co-infected ACE2-expressing cells. However, facing this potential recombination risk, the serum and antibody cross-reactivity against MERS/MERS-related coronaviruses after SARS-CoV-2 vaccination and/or infection is still elusive. Here, in this study, we showed that the serological cross-reactivity against MERS/MERS-related S proteins could be induced by SARS-CoV-2 infection but not by inactivated SARS-CoV-2 vaccination. Further investigation revealed that this serum cross-reactivity is due to monoclonals recognizing relatively conserved S2 epitopes, such as fusion peptide and stem helix, but not by antibodies against the receptor-binding domain (RBD), N-terminal domain (NTD) or subdomain-1 (SD1). Some of these anti-S2 cross-reactive mAbs showed cross-neutralizing activity, while none of them exhibited antibody-dependent enhancement (ADE) effect of viral entry in vitro. Together, these results dissected the SARS-CoV-2 infection-induced serological cross-reactivity against MERS/MERS-related coronaviruses, and highlighted the significance of conserved S2 region for the design and development of pan-β-coronaviruses vaccines.
Keywords: MERS-CoV; MERS-related coronavirus; S2 domain; SARS-CoV-2; cross-reactivity; neutralization.
. 2025 Mar 28:16:1541269.
doi: 10.3389/fimmu.2025.1541269. eCollection 2025. Anti-S2 antibodies responsible for the SARS-CoV-2 infection-induced serological cross-reactivity against MERS-CoV and MERS-related coronaviruses
Siyuan Sun[SUP] #[/SUP][SUP] 1 [/SUP], Jiaying He[SUP] #[/SUP][SUP] 2 [/SUP], Luotian Liu[SUP] #[/SUP][SUP] 1 [/SUP], Yuzhen Zhu[SUP] #[/SUP][SUP] 3 [/SUP], Qingsong Zhang[SUP] #[/SUP][SUP] 1 [/SUP], Yinong Qiu[SUP] #[/SUP][SUP] 1 [/SUP], Yuru Han[SUP] 1 [/SUP], Song Xue[SUP] 1 [/SUP], Xiaofang Peng[SUP] 1 [/SUP], Yiming Long[SUP] 1 [/SUP], Tianyu Lu[SUP] 1 [/SUP], Wei Wu[SUP] 1 [/SUP], Anqi Xia[SUP] 1 [/SUP], Yunjiao Zhou[SUP] 4 [/SUP], Yan Yan[SUP] 1 [/SUP], Yidan Gao[SUP] 1 [/SUP], Lu Lu[SUP] 1 [/SUP], Lei Sun[SUP] 1 [/SUP], Minxiang Xie[SUP] 1 [/SUP], Qiao Wang[SUP] 1 [/SUP]
Affiliations
- PMID: 40226608
- PMCID: PMC11985752
- DOI: 10.3389/fimmu.2025.1541269
Sarbecoviruses, such as SARS-CoV-2, utilize angiotensin-converting enzyme 2 (ACE2) as the entry receptor; while merbecoviruses, such as MERS-CoV, use dipeptidyl peptidase 4 (DPP4) for viral entry. Recently, several MERS-related coronaviruses, NeoCoV and PDF-2180, were reported to use ACE2, the same receptor as SARS-CoV-2, to enter cells, raising the possibility of potential recombination between SARS-CoV-2 and MERS-related coronaviruses within the co-infected ACE2-expressing cells. However, facing this potential recombination risk, the serum and antibody cross-reactivity against MERS/MERS-related coronaviruses after SARS-CoV-2 vaccination and/or infection is still elusive. Here, in this study, we showed that the serological cross-reactivity against MERS/MERS-related S proteins could be induced by SARS-CoV-2 infection but not by inactivated SARS-CoV-2 vaccination. Further investigation revealed that this serum cross-reactivity is due to monoclonals recognizing relatively conserved S2 epitopes, such as fusion peptide and stem helix, but not by antibodies against the receptor-binding domain (RBD), N-terminal domain (NTD) or subdomain-1 (SD1). Some of these anti-S2 cross-reactive mAbs showed cross-neutralizing activity, while none of them exhibited antibody-dependent enhancement (ADE) effect of viral entry in vitro. Together, these results dissected the SARS-CoV-2 infection-induced serological cross-reactivity against MERS/MERS-related coronaviruses, and highlighted the significance of conserved S2 region for the design and development of pan-β-coronaviruses vaccines.
Keywords: MERS-CoV; MERS-related coronavirus; S2 domain; SARS-CoV-2; cross-reactivity; neutralization.