Impaired Humoral Immunity Identified in Inactivated SARS-CoV-2 Vaccine Recipients without Anti-Spike RBD Antibodies

Inactivated SARS-CoV-2 vaccines have been deployed in a significant portion of the world population, who have widely varied responses to vaccination. Understanding this differential response would help the development of new vaccines for non-responders. Here, we conducted surveillance of anti-Spike receptor-binding domain (RBD) antibody levels in a large cohort of 534 healthy Chinese subjects vaccinated with two doses of inactivated SARS-CoV-2 vaccines. We show that the positive rate of antibodies among vaccinated subjects rapidly wanes as the interval between antibody testing and vaccination increases (14 to 119 days: 81.03%, 363 of 448 subjects; 120 to 149 days: 46.43%, 13 of 28 subjects; more than 150 days: 20%, 1 of 5 subjects). However, the antibodies were maintained at high levels in 16 convalescent COVID-19 patients at more than 150 days after recovery. We also found that increased age and body mass index are associated with decreased antibody levels. Vaccinated subjects who fail to produce antibodies display impaired B-cell activating humoral immunity, which was confirmed in COVID-19 patients without antibodies detected at 4 to 18 days after diagnosis. IMPORTANCE Our study illustrates the immune responses engaged by encountering antigen, highlighting the critical roles of B-cell activating humoral immunity in the body’s antibody production.