Cross-Neutralizing Antibody Responses to Diverse Coronaviruses in the Human Population

Area of Science:

• Virology
• Immunology
• Epidemiology

Background:

• The COVID-19 pandemic has altered population immunity.
• Understanding cross-neutralizing antibody responses against diverse coronaviruses post-pandemic is crucial.

Purpose of the Study:

• To evaluate serum neutralizing activity in individuals before and after the COVID-19 pandemic.
• To assess the breadth of cross-neutralizing antibody responses against various coronaviruses.

Main Methods:

• Serum samples from 869 individuals (78 pre-pandemic, 791 post-pandemic) from Wuhan, China were analyzed.
• Neutralizing activity against multiple sarbecoviruses, merbecoviruses, alphacoronaviruses, and MERS-CoV was measured.
• Antigenic mapping was employed to understand antibody-antigen relationships.

Main Results:

• Post-pandemic sera showed significantly enhanced neutralizing activity against sarbecoviruses and MjHKU4r-CoV-1 compared to pre-pandemic sera.
• Enhanced activity was most prominent against clade 1b sarbecoviruses, with mean viral inhibition increasing up to 76.5%.
• Khosta-2 was robustly neutralized by both cohorts, suggesting boosted cross-reactive immunity, primarily via S1-directed antibodies.

Conclusions:

• Post-pandemic sera exhibit broadened cross-neutralizing antibody responses, particularly against sarbecoviruses.
• This enhanced immunity may bolster population defense against related zoonotic coronaviruses.
• Increased population immunity could raise the barrier against the emergence of novel zoonotic sarbecoviruses in humans.