Key points

Current COVID-19 mRNA vaccine induces salivary and nasal SARS-CoV-2 specific IgG but not IgA production in children under 5 years of age

Mucosal anti-spike IgA is important for immune complex-mediated neutrophil extracellular trap formation against SARS-CoV-2 in the airway

Background Understanding antibody responses to SARS-CoV-2 vaccination is crucial for refining COVID-19 immunization strategies. Generation of mucosal immune responses, including mucosal IgA, could be of potential benefit to vaccine efficacy, yet limited evidence exists regarding the production of mucosal antibodies following the administration of current mRNA vaccines to young children.

Methods We measured the levels of antibodies against SARS-CoV-2 from a cohort of children under 5 years of age undergoing SARS-CoV-2 mRNA vaccination (serially collected, matched serum and saliva samples, N=116) or on convenience samples of children under 5 years of age presenting to a pediatric emergency department (nasal swabs, N=103). Further, we assessed salivary and nasal samples for the ability to induce SARS-CoV-2 spike-mediated neutrophil extracellular traps (NET) formation.

Results Longitudinal analysis of post-vaccine responses in saliva revealed the induction of SARS-CoV-2 specific IgG but not IgA. Similarly, SARS-CoV-2 specific IgA was only observed in nasal samples obtained from previously infected children with or without vaccination, but not in vaccinated children without a history of infection. In addition, oronasopharyngeal samples obtained from children with prior infection were able to trigger enhanced spike-mediated NET formation, and IgA played a key role in driving this process.

Conclusions Despite the induction of specific IgG in the oronasal mucosa, current intramuscular vaccines have limited ability to generate mucosal IgA in young children. These results confirm the independence of mucosal IgA responses from systemic humoral responses following mRNA vaccination and suggest potential future vaccination strategies for enhancing mucosal protection in this young age group.

David Walt has a financial interest in Quanterix Corporation, a company that develops an ultra-sensitive digital immunoassay platform. He is an inventor of the Simoa technology, a founder of the company, and also serves on its Board of Directors. Dr. Walt's interests were reviewed and are managed by Brigham and Women's Hospital and Partners Healthcare in accordance with their conflict-of-interest policies.

This study was funded by NIH/NHLBI #5K08HL143183, and the Chan-Zuckerberg Initiative.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

IRB of Massachusetts General Hospital gave ethical approval for this work. IRB of Boston Children's Hospital gave ethical approval for this work.

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All data produced in the present study are available upon reasonable request to the authors.