Anti-S2 antibodies responsible for the SARS-CoV-2 infection-induced serological cross-reactivity against MERS-CoV and MERS-related coronaviruses

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 28, 2025

Sarbecoviruses, such as SARS-CoV-2, utilize angiotensin-converting enzyme 2 (ACE2) the entry receptor; while merbecoviruses, MERS-CoV, use dipeptidyl peptidase 4 (DPP4) for viral entry. Recently, several MERS-related coronaviruses, NeoCoV and PDF-2180, were reported to ACE2, same receptor enter cells, raising possibility of potential recombination between SARS-CoV-2 coronaviruses within co-infected ACE2-expressing cells. However, facing this risk, serum antibody cross-reactivity against MERS/MERS-related after vaccination and/or infection is still elusive. Here, in study, we showed that serological S proteins could be induced by but not inactivated vaccination. Further investigation revealed due monoclonals recognizing relatively conserved S2 epitopes, fusion peptide stem helix, antibodies receptor-binding domain (RBD), N-terminal (NTD) or subdomain-1 (SD1). Some these anti-S2 cross-reactive mAbs cross-neutralizing activity, none them exhibited antibody-dependent enhancement (ADE) effect vitro. Together, results dissected infection-induced highlighted significance region design development pan-β-coronaviruses vaccines.

Язык: Английский

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RBD-depleted SARS-CoV-2 spike generates protective immunity in cynomolgus macaques

npj Vaccines, Год журнала: 2025, Номер 10(1)

Опубликована: Март 30, 2025

Abstract The SARS-CoV-2 pandemic revealed the rapid evolution of circulating strains. This led to new variants carrying mostly mutations within receptor binding domain, which is immunodominant upon immunization and infection. In order steer immune response away from RBD epitopes more conserved domains, we generated S glycoprotein trimers without stabilized them by formaldehyde cross-linking. cryoEM structure demonstrated that SΔRBD folds into native prefusion conformation, one specific cross-link between S2 protomers. was coated onto lipid vesicles, produce synthetic virus-like particles, SΔRBD-LV, were utilized in a heterologous prime-boost strategy. Immunization cynomolgus macaques either three times with mRNA Comirnaty vaccine or two followed SΔRBD-LV showed boost induced similar antibody titers neutralization different variants, including omicron. Upon challenge omicron XBB.3, both only Comirnaty/SΔRBD-LV vaccination schemes conferred overall protection infection for schemes. However, indicated better against lung than strategy alone. Together our findings indicate highly immunogenic provides improved compared third indicative superior antibody-based protection.

Язык: Английский

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Structural basis and mode of action for two broadly neutralizing nanobodies targeting the highly conserved spike stem-helix of sarbecoviruses including SARS-CoV-2 and its variants

PLoS Pathogens, Год журнала: 2025, Номер 21(4), С. e1013034 - e1013034

Опубликована: Апрель 11, 2025

The persistent emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants highlights the need for developing broad-spectrum antiviral agents. Here, we report identification two sarbecovirus S2-specific alpaca nanobodies, namely H17 and H145, that effectively neutralize known SARS-CoV-2 (including Omicron subvariants) other sarbecoviruses (such as SARS-CoV, PANG/GD, WIV1, HKU3). nanobodies recognize a linear epitope (D 1139 PLQPELDSFKEEL 1152 ) in upper region S2 stem-helix (SH), which is highly conserved among sarbecoviruses. complex structure nanobody bound to SH-peptide reveal binding will impede refolding S2, neutralizing virus. Moreover, bind viral an acidification-insensitive manner, demonstrating their capacity entry inhibition especially when viruses enter via endosomal route. Finally, H145 possess better taking-action window virus neutralization, superior RBD-targeting exert neutralization by competing against ACE2 binding. Taken together, results suggest anti-SH are promising drug candidates preventing treating pandemic infections

Язык: Английский

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Low Antibody-Dependent Enhancement of Viral Entry Activity Supports the Safety of Inactivated SARS-CoV-2 Vaccines

Vaccines, Год журнала: 2025, Номер 13(4), С. 425 - 425

Опубликована: Апрель 18, 2025

Background/Objectives: The antibody-dependent enhancement (ADE) of viral entry has been documented for SARS-CoV-2 infection both in vitro and vivo. However, the potential vaccination to elicit similar ADE effects remains unclear. Methods: In this study, we assessed monoclonal antibodies (mAbs) derived from individuals vaccinated with inactivated vaccine compared them those one convalescent donor. Results: Our analysis revealed no significant difference binding affinity or neutralizing capacity between mAbs. induced fewer ADE-inducing mAbs, particularly targeting Class III epitope on receptor-binding domain (RBD) individual. Moreover, was detected either sera, indicating low levels sera. Conclusions: An induces natural infection, further emphasizing safety vaccines.

Язык: Английский

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Making Universal Vaccines and Antibodies Through Glycoengineering

Methods in molecular biology, Год журнала: 2025, Номер unknown, С. 35 - 50

Опубликована: Янв. 1, 2025

Язык: Английский

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