Enhanced SARS-CoV-2 neutralization by dimeric IgA

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), primarily infects cells at mucosal surfaces. Serum neutralizing antibody responses are variable and generally low in individuals that suffer mild forms of COVID-19. Although potent immunoglobulin G (IgG) antibodies can neutralize the virus, less is known about secretory antibodies such as IgA that might affect the initial viral spread and transmissibility from the mucosa. Here, we characterize the IgA response to SARS-CoV-2 in a cohort of 149 convalescent individuals after diagnosis with COVID-19. IgA responses in plasma generally correlated with IgG responses. Furthermore, clones of IgM-, IgG-, and IgA-producing B cells were derived from common progenitor cells. Plasma IgA monomers specific to SARS-CoV-2 proteins were demonstrated to be twofold less potent than IgG equivalents. However, IgA dimers, the primary form of antibody in the nasopharynx, were, on average, 15 times more potent than IgA monomers against the same target. Thus, dimeric IgA responses may be particularly valuable for protection against SARS-CoV-2 and for vaccine efficacy.

Automated summary

The IgA response to SARS-CoV-2 was characterized in a cohort of 149 convalescent individuals after COVID-19 diagnosis. IgA responses in plasma generally correlated with IgG responses, and B cells producing IgM, IgG, and IgA were derived from common progenitor cells. Notably, IgA dimers were found to be 15 times more potent than IgA monomers against SARS-CoV-2, suggesting their potential value for protection and vaccine efficacy.