Anti-Spike Antibody Response to Natural Infection with SARS-CoV-2 and Its Activity against Emerging Variants

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has substantially affected human health globally. Spike-specific antibody response plays a major role in protection against SARS-CoV-2 infection. Here, we examined serological anti-spike antibody and memory B cell responses in adults with acute SARS-CoV-2 infection. Twenty-five adult patients were enrolled between January and September 2020, and 21 (84%) had a detectable spike-binding antibody response in serum on day 21 +/- 8 (6 to 33) after the onset of illness. Among those with positive spike-binding antibody response, 19 (90%) had a positive hemagglutination titer and 15 (71%) had angiotensin-converting enzyme 2 (ACE2)-blocking serological activities. Follow-up serum samples collected 11 +/- 1 (7 to 15) months after infection exhibited an average of 2.6 6 +/- 1.0 (1.0 to 3.5)-fold reduction in the spike-binding antibody response. Moreover, convalescent and follow-up serum samples showed 83 +/- 6 82 (15 to 306)- and 165 +/- 167 (12 to 456)-fold reductions in the neutralization activity against the Omicron variant, respectively. Upon acute infection, spike-specific memory B cell responses were elicited, with an average frequency of 1.3% +/- 6 1.2% of peripheral B cells on day 19 +/- 7 (6 to 33) after the onset of illness. IgM memory B cells were predominantly induced. Patients with fever and pneumonia showed significantly stronger spike-binding, ACE2-blocking antibody, and memory B cell responses. In conclusion, spike-specific antibody response elicited upon acute SARS-CoV-2 infection may wane over time and be compromised by the emergence of viral variants. IMPORTANCE As spike protein-specific antibody responses play a major role in protection against SARS-CoV-2, we examined spike-binding and ACE2-blocking antibody responses in SARS-CoV-2 infection at different time points. We found robust responses following acute infection, which waned approximately 11 months after infection. Patients with fever and pneumonia showed significantly stronger spike-binding, ACE2-blocking antibody, and memory B cell responses. In particular, spike-specific antibody response in the convalescent and follow-up serum samples was substantially affected by emerging variants, especially Beta and Omicron variants. These results warrant continued surveillance of spike-specific antibody responses to natural infections and highlight the importance of maintaining functional anti-spike antibodies through immunization.