Anti-spike mucosal IgA protection against SARS-CoV-2 Omicron infection

To the editor:

Mucosal IgA could present immunity against respiratory viruses.1 Vaccination against extreme acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enhances mucosal IgA responses,two and neutralizing IgA, together with neutralizing IgA against the B.1.1.529 (omicron) variant of SARS-CoV-2, was detected after infection with wild-type SARS-CoV-2.3 However, the potential position of mucosal IgA in protection against SARS-CoV-2 infection continues to be unknown.

Spike-specific mucosal IgA and Omicron infection.

Panel A exhibits the screening and follow-up of well being employees on this research. Participants underwent polymerase chain response (PCR) testing of nasal, oropharyngeal, and salivary swab samples twice weekly for 4 weeks. Mucosal antibody ranges had been decided from nasal swab samples obtained at baseline in all members and through and after subsequent micron infection (57 members) (decided 5 weeks after the booster dose). Panel B exhibits wild-type (WT) particular mucosal IgA ranges at baseline. Thick horizontal bars present the median, and skinny horizontal bars present the twenty fifth and seventy fifth percentiles. (For members with out prior infection, the median and twenty fifth percentile had been each 0.1 arbitrary models. [AU] per milliliter.) Participants who had been PCR-positive for SARS-CoV-2 at baseline weren’t included within the plot. Panel C exhibits the relative danger of microinfection and the distinction in viral replication (measured as cycle nadir) [Ct]) amongst members with increased WT-specific mucosal IgA or IgG ranges at baseline (outlined as these within the (≥seventy fifth percentile)) in comparison with members with decrease ranges (

We evaluated SARS-CoV-2-specific mucosal antibody responses in 338 tri-vaccinated HCWs (Table S1 within the Supplementary Appendix, the complete textual content of this letter is obtainable at NEJM.org) between January and February 2022 in a weekly quantitative polymerase chain response screening research.4 Mucosal antibody responses had been assessed over time in 57 members contaminated with the omicron variant at screening (Figure 1A). Mucosal IgA and IgG responses had been analyzed in relation to beforehand obtained serological and viral information.4

Wild-type SARS-CoV-2 spike-specific mucosal IgA and IgG had been detected in 210 members (62%) and 337 members (>99%), respectively (fig. S1A and S1B). Spike-specific mucosal IgA ranges (Figure 1B) however not IgG (fig. S1C) was increased amongst members with earlier SARS-CoV-2 infection than amongst these with out earlier infection (P<0.001). Primary vaccine routine, time between the third vaccine dose and sampling time, age, and gender didn't considerably have an effect on wild-type spike-specific mucosal IgA ranges (desk S2).

Next, we evaluated the potential protecting results of mucosal antibodies against omeron infection and viral replication. Participants with excessive wild-type spike-specific mucosal IgA ranges (outlined on the seventy fifth percentile) at enrollment had a considerably decrease danger of subsequent omicron infection than these with low ranges (relative danger, 0.35; 97.5%). confidence interval [CI]from 0.11 to 0.91) (Figure 1C and Table S3); this impact was not discovered amongst members with increased IgG ranges at admission. Results had been comparable amongst members with and with out prior infection (fig. S2 and desk S4). At baseline, omicron sublineage BA.1 spike-specific mucosal IgA ranges had been typically decrease than wild-type spike-specific mucosal IgA ranges (fig. S1). However, a small however nonsignificantly decrease danger of subsequent omicron infection was noticed amongst members with increased BA.1 spike-specific mucosal IgA ranges than these with decrease baseline ranges (relative danger, 0.63; 97.5% CI, 0.22 to 1.49 ). We additionally noticed a considerably decrease stage of viral replication amongst contaminated members with increased baseline ranges of wild-type-specific mucosal IgA (distinction in nadir cycle threshold worth, 3.91; 97.5% CI, −0.87 to eight.70) (Figure 1C and Table S5); this impact was not discovered amongst members with increased IgG ranges.

We analyzed the kinetics of mucosal antibody responses after micron infection. In each beforehand contaminated and uninfected members, spike-specific, receptor-binding domain-specific, and nucleocapsid-specific mucosal IgA ranges elevated over time after infection (Figure 1D and Fig. S3). This result’s completely different from the outcomes of current research of our group4 and Reynolds et al.,5 This primarily demonstrated omicron-induced enhancement of systemic spike-specific IgG responses in beforehand uninfected members. Wild-type spike-specific mucosal IgA ranges weren’t associated to wild-type spike-specific mucosal or serum IgG ranges (fig. S4A and S4B). However, a robust correlation was noticed between spike-specific serum ranges and mucosal IgG (Spearman’s r=0.7, P<0.001) (fig. S4C), confirming that mucosal “shed” IgG from the circulation.1

Taken collectively, these findings recommend that wild-type SARS-CoV-2 spike-specific mucosal IgA is protecting against omicron infection. Further research are warranted to find out whether or not vaccines that induce a mixture of mucosal and systemic immune responses can present stronger protection than intramuscular vaccines.

Sebastian Haverwall, MD
Ulrika Marking, MD
Julia Svensson, M.D.
Nina Greilert-Norin, RN
Karolinska Institutet, Stockholm, Sweden

Philip Bacchus, M.Sc.
Swedish Armed Forces, Umeå, Sweden

Peter Nilsson, Ph.D.
Sophia Hober, Ph.D.
KTH Royal Institute of Technology, Stockholm, Sweden

Max Gordon, Ph.D.
Karolinska Institutet, Stockholm, Sweden

Kim Blom, Ph.D.
Jonas Klingström, Ph.D.
Swedish Public Health Agency, Solna, Sweden

Mikael Aberg, Ph.D.
Uppsala University, Uppsala, Sweden

Anna Smed-Sørensen, candidate of medical sciences.
Charlotte Talin, Ph.D.
Karolinska Institutet, Stockholm, Sweden
[email protected]

Supported by grants from the Jonas and Kristina af Joknik Foundation (to Dr. Thalin), the Stockholm Region (to Dr. Thalin), the Knut and Alice Wallenberg Foundation (to Drs. Thalin, Aberg, and Klingström), and the Leif Lundblad Family Foundation. (to Dr. Thalin), the Swedish Research Council (to Dr. Smed-Sørensen), the Swedish Heart and Lung Foundation (to Dr. Smed-Sørensen), the Bill & Melinda Gates Foundation (to Dr. Smed-Sørensen), and the Center for Innovative Medicine (to Drs. Blom and Klingström).

Disclosure types supplied by the authors can be found at NEJM.org, together with the complete textual content of this letter.

This letter was revealed on September 14, 2022 at NEJM.org.

Dr. Havervall, Marking, Klingström, Aberg, Smed-Sørensen, and Talin contributed equally to this letter.

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  3. 3. C plateaus, Fernandes I, Bruel T, and so on. Human SARS-CoV-2-neutralizing IgA and IgG antibodies efficient against BA.1 and BA.2 omicrons. J Exp Med 2022219(7):e20220638e20220638.

  4. 4. Blom Okay, Marking U, Haverwall S, and so on. Immune responses following omicron infection in triple-vaccinated healthcare employees with and with out prior SARS-CoV-2 infection. Lancet Infect Dis 202222:943945.

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