TOPLINE

Higher baseline nasal antigen-specific IgA was associated with markedly lower risk for influenza A H1N1 and SARS-CoV-2 over 4 months of home-based quantitative polymerase chain reaction (qPCR) surveillance. Intramuscular influenza and SARS-CoV-2 vaccination increased serum immunoglobulin (Ig)G but not nasal IgA and did not reduce risk for mild infection.

METHODOLOGY

• Researchers conducted a prospective cohort study to evaluate whether antigen-specific mucosal IgA protects against influenza A H1N1 infection, and to compare nasal IgA and serum IgG as correlates of protection against subsequent influenza.
• They enrolled 926 healthcare workers from the ongoing COMMUNITY cohort in Stockholm, Sweden, for 4 months of prospective surveillance during the 2023-2024 influenza season.
• Participants provided baseline nasal secretion and serum samples in December 2023 for measurement of H1-specific nasal IgA (1:1000 dilution) and serum IgG (1:50,000 dilution) levels. Participants self-collected nasal, oropharyngeal, and saliva samples at symptom onset for home-based qPCR testing for influenza A H1N1 and SARS-CoV-2 infection (internal comparator).
• Antibody concentrations were measured using electrochemiluminescence immunoassays optimized for mucosal sampling. Poisson regression models (with log time at risk as offset) assessed associations between baseline antibody levels, recent vaccination, and subsequent infection, adjusting for age, sex (where applicable), nasal IgA, and serum IgG.

TAKEAWAY

• Influenza A H1N1 and SARS-CoV-2 infections increased antigen-specific nasal IgA (median fold change, 8.0 [P = .007] and 3.0 [P < .001], respectively) and serum IgG levels (median fold change, 4.5 and 2.5, respectively; P < .001 for both) 4-6 months after infection.
• Antigen-specific serum IgG levels increased after both seasonal influenza and SARS-CoV-2 vaccinations (P < .001), but antigen-specific nasal IgA levels decreased after both influenza vaccination (P = .015) and SARS-CoV-2 vaccination (P = .006).
• Baseline nasal H1-specific IgA above the median was linked to a lower risk for H1N1 infection (incidence rate ratio [IRR], 0.23; P = .026) and each twofold increase in baseline nasal H1-specific IgA was associated with a lower risk for H1N1 infection (IRR, 0.69; P = .014). Baseline serum H1-specific IgG was not linked to a lower risk for H1N1 infection; in contrast, higher baseline spike-specific serum IgG was associated with a lower risk for SARS-CoV-2 infection (P = .012), though a doubling of baseline levels was not.
• Recent (within 30 days prior to baseline sampling) influenza and SARS-CoV-2 vaccination increased antigen-specific serum IgG levels (P < .001 for both) compared with no vaccination but did not increase nasal IgA levels in the respiratory mucosa. Recent vaccination was also not associated with a lower risk for subsequent H1N1 or SARS-CoV-2 infections.

IN PRACTICE

“Our findings furthermore underscore the importance of antigen- specific mucosal IgA in protection against infection with influenza A virus and SARS-CoV-2, both of which entail a high pandemic potential. Strategies focusing on the generation of robust respiratory mucosal IgA responses are urgently needed to reduce infection rates and serve as a pandemic preparedness measure,” the authors of the study concluded.

SOURCE

The study was led by Oscar Bladh, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet in Stockholm, Sweden. It was published online on June 30, 2026, in eBioMedicine.

LIMITATIONS

The relatively small number of influenza A H1N1 infections limited statistical power to define a specific protective threshold for mucosal IgA and precluded robust subtype-specific analyses for other influenza viruses. Functional neutralization assays on nasal secretions could not be performed. Symptom severity, exposure history, and personal protective equipment use were not measured in detail.

DISCLOSURES

The study was funded by grants from the European Research Council, the Swedish Society for Medical Research, the Knut and Alice Wallenberg Foundation, and the SciLifeLab Pandemic Laboratory Preparedness Program. One author reported patents, consulting, royalty payments, and company relationships related to influenza and SARS-CoV-2 vaccines or assays. The remaining authors reported no conflicts of interest. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.