Role of Immunoglobulin M and A Antibodies in the Neutralization of Severe Acute Respiratory Syndrome Coronavirus 2

Abstract

Background SARS-CoV-2 has infected millions of people globally. Virus infection requires the receptor-binding domain (RBD) of the spike protein. Although studies have demonstrated anti-spike and -RBD antibodies to be protective in animal models, and convalescent plasma as a promising therapeutic option, little is known about immunoglobulin (Ig) isotypes capable of blocking infection. Methods We studied spike- and RBD-specific Ig isotypes in convalescent and acute plasma/sera using a multiplex bead assay. We also determined virus neutralization activities in plasma, sera, and purified Ig fractions using a VSV pseudovirus assay. Results Spike- and RBD-specific IgM, IgG1, and IgA1 were produced by all or nearly all subjects at variable levels and detected early after infection. All samples displayed neutralizing activity. Regression analyses revealed that IgM and IgG1 contributed most to neutralization, consistent with IgM and IgG fractions’ neutralization potency. IgA also exhibited neutralizing activity, but with lower potency. Conclusion IgG, IgM and IgA are critical components of convalescent plasma used for COVID-19 treatment.

Clinical predictors of SARS‐CoV‐2 neutralizing antibody titers in COVID‐19 convalescents: Implications for convalescent plasma donor recruitment

“…On average, the nAb titer peaks 30 days after symptom onset and declines by 25% every 15 days 17 (largely due to the decline in neutralizing IgM and IgA) 29,30 . It is therefore sounding that the days since positive nasopharyngeal swab correlates with the nAb titer.…”

Know your enemy or find your friend?—Induction of IgA at mucosal surfaces

“…When it comes to virus neutralization it is still unclear what role IgA plays. Some studies have reported that SARS‐CoV‐2‐specific IgA antibody levels in serum show a better correlation with the ability of the serum to neutralize SARS‐CoV‐2 than IgG levels do, 210,220,221 at least early during the response but other studies have come to the opposite conclusion 155,222,223 . Another found that IgA in nasal washes efficiently neutralized SARS‐CoV‐2 219 .…”

Human IgG and IgA responses to COVID-19 mRNA vaccines

“…Humoral responses are key components of adaptive immunity to viral infection [1]. Both alpha and gamma immunoglobulins (Ig) from COVID-19 patients mediate viral neutralization and may play distinct roles in immunity during different phases of infection and at specific anatomical sites [2][3][4][5]. IgA is the most abundantly produced Ig in humans (66 gm/kg/day) and the most abundant isotype at mucosal sites while IgG is major isotype in blood and most tissues [6,7].…”