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SARS-CoV-2 S2-targeted vaccination elicits broadly neutralizing antibodies.

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journal contribution
posted on 01.08.2022, 10:04 authored by Kevin W Ng, Nikhil Faulkner, Katja Finsterbusch, Mary Wu, Ruth Harvey, Saira Hussain, Maria Greco, Yafei Liu, Svend Kjaer, Charles Swanton, Sonia Gandhi, Rupert Beale, Steve J Gamblin, Peter Cherepanov, John McCauley, Rodney Daniels, Michael Howell, Hisashi Arase, Andreas Wack, David LV Bauer, George Kassiotis
Several variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged during the current coronavirus disease 2019 (COVID-19) pandemic. Although antibody cross-reactivity with the spike glycoproteins (S) of diverse coronaviruses, including endemic common cold coronaviruses (HCoVs), has been documented, it remains unclear whether such antibody responses, typically targeting the conserved S2 subunit, contribute to protection when induced by infection or through vaccination. Using a mouse model, we found that prior HCoV-OC43 S-targeted immunity primes neutralizing antibody responses to otherwise subimmunogenic SARS-CoV-2 S exposure and promotes S2-targeting antibody responses. Moreover, vaccination with SARS-CoV-2 S2 elicited antibodies in mice that neutralized diverse animal and human alphacoronaviruses and betacoronaviruses in vitro and provided a degree of protection against SARS-CoV-2 challenge in vivo. Last, in mice with a history of SARS-CoV-2 Wuhan-based S vaccination, further S2 vaccination induced broader neutralizing antibody response than booster Wuhan S vaccination, suggesting that it may prevent repertoire focusing caused by repeated homologous vaccination. These data establish the protective value of an S2-targeting vaccine and support the notion that S2 vaccination may better prepare the immune system to respond to the changing nature of the S1 subunit in SARS-CoV-2 variants of concern, as well as to future coronavirus zoonoses.

Funding

Crick (Grant ID: 10099, Grant title: Kassiotis FC001099) Crick (Grant ID: 10030, Grant title: McCauley FC001030) Crick (Grant ID: 11104, Grant title: Bauer FC011104) Crick (Grant ID: 10827, Grant title: Beale FC001827) Crick (Grant ID: 10061, Grant title: Cherepanov FC001061) Crick (Grant ID: 10078, Grant title: Gamblin FC001078) Crick (Grant ID: CC1071, Grant title: STP High Throughput Screening) Crick (Grant ID: CC1068, Grant title: STP Structural Biology) Crick (Grant ID: 10169, Grant title: Swanton FC001169) Crick (Grant ID: 10206, Grant title: Wack FC001206)

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