bioRxiv : the preprint server for biology · 2026
Protective pan-betacoronavirus neutralizing antibodies by vaccination.
СтатьяПрепринтНазвание и аннотация: Перевод в очереди
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Zhou Panpan, Feng Ziqi, He Wan-Ting, Zhu Yuxin, Yuan Meng, Li Xuduo, Zhang Yuexiu, Vo Lina, Capozzola Tazio, Callaghan Sean, Mishra Nitesh, Avillion Gabriel, Dueker Katharina, Liang Bo, Roy Chowdhury Rohan, Nedellec Rebecca, Lee Wen-Hsin, Allen Joel D, Walsh Agnes, Melo Mariane, McAnarney Eileen T, Kumar Nisha Asok, Rinaldi William, Ferguson Melissa, Crispin Max M, Ward Andrew B, Irvine Darrell J, Alameh Mohamad-Gabriel, Weissman Drew, Baric Ralph S, Gralinski Lisa E, Wilson Ian A, Burton Dennis R, Andrabi Raiees
Аннотация
UNLABELLED: The continued emergence of betacoronaviruses underscores the urgent need for vaccines that provide broadly protective immunity. Here, we present an epitope-focused vaccine strategy targeting the conserved S2 stem-helix region of the spike fusion machinery, a broadly neutralizing antibody-(bnAb) epitope shared across betacoronaviruses yet partially occluded on the native spike. Immunization of non-human primates with engineered S2 stem-helix nanoparticle immunogens, alone or followed by a SARS-CoV-2 BA.1 spike mRNA boost, elicited broadly cross-reactive antibody responses against sarbecoviruses, merbecoviruses, and embecoviruses and neutralized SARS-CoV-2, multiple variants, other sarbecoviruses, and MERS-CoV. Vaccine-elicited monoclonal antibodies displayed broad in-vitro neutralizing activity and protected against both SARS-CoV-2 and MERS-CoV in-vivo . Structural analyses revealed conserved features between rhesus and human stem-helix bnAbs, supporting the translational potential. Overall, our findings provide proof-of-concept that epitope-focused nanoparticle immunogens can target partially occluded, immunoquiescent bnAb epitopes, laying the groundwork for pan-betacoronavirus vaccines that provide broad protection and strengthen pandemic preparedness.
ONE SENTENCE SUMMARY: Epitope-focused S2 stem-helix nanoparticle immunogens elicit protective broadly neutralizing antibodies (bnAbs) against diverse betacoronaviruses in non-human primates, establishing a framework for development of pan-betacoronavirus vaccines.
ONE SENTENCE SUMMARY: Epitope-focused S2 stem-helix nanoparticle immunogens elicit protective broadly neutralizing antibodies (bnAbs) against diverse betacoronaviruses in non-human primates, establishing a framework for development of pan-betacoronavirus vaccines.