A new study of more than 150 COVID-19 patients shows that IgA antibodies dominate the early response to the SARS-CoV-2 virus, coming on more quickly and strongly than IgG and IgM antibodies. This is a somewhat unexpected result, as IgM antibodies are usually the immune system's first responders. The finding may also inform the development of vaccines that encourage the IgA response, as well as IgA-based tests to detect infection at early stages, Delphine Sterlin and colleagues say. The researchers measured antibody responses in blood, saliva, and fluid from a broncho-alveolar wash in the patients, whose disease symptoms ranged in severity. They found that IgA concentrations were higher than IgG and IgM concentrations in these fluids for the first 3 to 4 weeks after the first appearance of symptoms and then waned, but IgA persisted in saliva for several more weeks. The surge in IgA was associated with an increase in IgA-secreting cells called plasmablasts, which can preferentially target the mucosal surfaces in the respiratory tract that the virus attacks. Sterlin et al. also found that IgA was more potent than IgG at neutralizing SARS-CoV-2.
In a separate, unrelated study, Zijun Wang and colleagues took a closer look at IgA responses to SARS-CoV-2 in 149 individuals recovering from COVID-19. After cloning antibodies taken from the patients, Wang et al. discovered that the dimeric form of IgA - consisting of two IgA molecules linked together - was roughly fifteen times better at neutralizing the SARS-CoV-2 virus than the monomeric form. Dimeric IgA is typically considered the most prevalent antibody isotype in mucosal tissues of the upper respiratory tract, a major point of entry for the virus. Given the potency of the dimeric IgA antibodies, Wang et al. suggest that a vaccine designed to induce dimeric IgA, perhaps delivered orally or nasally to target mucosal tissues, could offer protection against the virus.
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Science Translational Medicine