SARS-CoV-2 Vaccination Provides Boosted Mucosal Protection in Previously Infected Young Children

Abstract Text: Understanding the basis for generation of protective humoral responses to SARS-CoV-2 vaccination in young children is critical for refining immunization strategies and minimizing the severity of COVID-19. It has been suggested that generation of mucosal IgA could improve the efficacy of vaccines directed at viral respiratory pathogens, however evidence regarding the production of mucosal IgA in children who received current SARS-CoV-2 mRNA vaccines is quite limited. To delineate the generation of mucosal IgA responses following vaccination and/or natural infection in young children, we assessed mucosal IgA responses in saliva (n=116) and nasal swabs (n=103) of children under 5 years of age stratified by vaccination status and history of prior SARS-CoV-2 infection. Analysis of serial matched serum and saliva specimens following SARS-CoV-2 mRNA vaccination revealed that despite robust IgG responses in the serum, post-vaccination IgA responses in saliva were significantly higher in children with a history of COVID-19 infection. Similarly, analysis of nasal swabs obtained from a convenience sample of young children demonstrated that SARS-CoV-2 specific IgA levels were significantly higher in children with a history of COVID-19, or both a history of COVID-19 and SARS-CoV-2 vaccination, than in children with SARS-CoV-2 vaccination without prior COVID-19 disease. These results indicate that the ability of current SARS-CoV-2 mRNA vaccines to generate mucosal IgA responses is quite limited in young children who have not previously had COVID-19. This study highlights the importance of considering both mucosal and circulating responses when evaluating vaccine-induced humoral immunity in pediatric populations.