Systemic and mucosal IgA responses are variably induced in response to SARS-CoV-2 mRNA vaccination and are associated with protection against subsequent infection

Abstract

SARS-CoV-2 is a novel respiratory virus that has quickly spread across the globe. The virus uses a protein called Spike and its associated receptor binding domain (RBD) to interact with angiotensin converting enzyme-2 (ACE-2) on the surface of epithelial cells in the respiratory tract. Although a definite correlate of protection against COVID-19 has yet to emerge, many studies have quantified anti-Spike and anti-RBD IgG antibody (Ab) levels, as well as neutralizing Ab in the blood to ascertain immunity. This approach misses out on Ab that are produced in the upper respiratory tract (URT) mucosa – the site of viral encounter. Whether intramuscularly (i.m.) administered COVID-19 vaccines can promote immunity in the mucosa is not well understood. We recently completed a study where we showed that anti-Spike/RBD IgG could be detected in the saliva following i.m. vaccination with either two doses of mRNA vaccines (Pfizer or Moderna) or with a heterologous dosing of Astra Zeneca followed by an mRNA vaccine. Administration of a second dose of mRNA boosted the IgG but not IgA response, with only 30% of participants remaining positive for IgA at this timepoint. At 6 months post-dose 2, these participants had diminished anti-Spike/RBD IgG levels, although secretory component associated anti-Spike Ab were more stable. Examining two prospective cohorts we found that participants who experienced breakthrough infections with SARS-CoV-2 had lower levels of vaccine-induced serum anti-Spike/RBD IgA at 2–4 weeks post-dose 2 compared to participants who did not experience an infection, whereas IgG levels were comparable between groups. These data suggest that COVID-19 vaccines that elicit a durable IgA response may have utility in preventing infection. We received funding support from CIHR (Fund #15992), a COVID-19 Immunity Task force grant, an “Ontario Together” province of Ontario grant, a CIHR team grant to CoVARR-Net, a Donation from the Royal Bank of Canada (RBC) and a donation from the Krembil Foundation to the Sinai Health System Foundation.

Long-term systemic and mucosal SARS-CoV-2 IgA response and its association with persistent smell and taste disorders

“…After vaccination, Spike, Spike/NTD and Spike/RBD positively correlated with neutralizing antibodies, as observed in other cohorts (45), but we also noticed a positive correlation with Spike/NTD in saliva. In previous studies, a detectable neutralizing activity in saliva observed 2 to 4 weeks post-vaccination was described low and transient with a rapid decline (16, 47). The ratio of saliva/serum IgA clearly showed two differential profiles according to previous COVID-19 status.…”

“…Vaccination with mRNA or Adenovirus-vectored vaccines reactivated a mucosal response in previously infected individuals but failed to induce a significant mucosal response in naive individuals, as already observed on a more limited cohort (25). As breakthrough infections have been correlated with IgA levels (16), IgA production may be a key point to address the issue of controlling the infection locally and preventing the transmission from vaccinated individuals. Most efficient vaccine platforms or route of administration inducing mucosal immunity are needed in the future for COVID-19 control, as already shown in preclinical studies (7, 9).…”

“…Natural polyreactive IgA with cross-reactivity and low affinity have also been described in the lumen of mucosal surfaces (13). In contrast to nasal or bronchoalveolar samples, saliva is an easy-toaccess biofluid where specific SARS-CoV-2 IgA have been detected (14)(15)(16), providing information about the mucosal response by harboring a significant population of IgA-secreting plasma cells.…”