Postdoctoral Research Fellow Dana-Farber Cancer Inst. Boston, Massachusetts, United States
Introduction/Rationale: As the evolution of SARS-CoV-2 continues, the emergence of antigenically distinct variants capable of immune escape has raised significant concerns regarding vaccine design. Moreover, a deeper understanding of heterologous exposures by vaccination and prior infection that contribute to the development of broadly neutralizing antibodies holds considerable promise for enhancing vaccine design and strengthening our adaptive immunity. Here we report that heterologously boosted hybrid immunity results in enhanced cross-reactive neutralizing antibodies.
Methods: We collected blood samples from participants who had recovered from COVID-19 at various time points. Based on their vaccination types, we categorized them into four groups. We measured the titers of antibodies against SARS-CoV-2 variant spikes and HCoV-OC43 spikes using ELISA and analyzed the data through antigenic cartography. Additionally, we conducted a pseudovirus neutralization assay to investigate the anti-viral activities of the antibodies from each group.
Results: We isolated cross-reactive monoclonal antibodies against SARS-CoV-2 and HCoV-OC43 spikes from the serum of a participant who was vaccinated against the Wuhan-Hu-1 strain and later infected with the Omicron variant. Notably, one of these monoclonal antibodies, designated F4, demonstrated the broadest reactivity and neutralizing activity against β-coronaviruses, binding specifically to the fusion peptide region of SARS-CoV-2 spike. Structural modeling suggests that mutations in F4 are critical for its binding to the fusion peptide.
Conclusion: In summary, our study suggests that heterologous boosting with different SARS-CoV-2 variants can elevate a titer of cross-reactive neutralizing antibodies, paralleling an antigenic shift towards β-coronaviruses. These findings will provide valuable insights into the potential of a heterologous boosting strategy and contribute to the development of a universal vaccine approach targeting β-coronaviruses.
