Human dimeric IgA antibodies are potent neutralizers of SARS-CoV-2. Two is better than one for COVID-19 Most individuals that become infected with SARS-CoV-2, the virus that causes COVID-19, produce neutralizing antibodies against the virus. However, the relative contribution of individual antibody isotypes remains unclear. In this study, Wang et al . investigated the function of SARS-CoV-2–specific antibodies of the IgA isotype, which exists in both monomeric and dimeric forms. Dimeric IgA antibodies, which are formed by the covalent linkage of two individual IgA monomers, are predominantly found in mucosal tissues, including the upper respiratory tract where SARS-CoV-2 is first encountered. The authors found that dimeric IgA antibodies neutralized SARS-CoV-2 more effectively than their monomeric counterparts. Thus, vaccines that induce dimeric IgA antibodies at mucosal surfaces may be good candidates for protection against SARS-CoV-2. 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.
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