Sequential intranasal booster triggers class switching from intramuscularly primed IgG to mucosal IgA against SARS-CoV-2.

Summary

An IFN-armed protein vaccine regimen with intramuscular priming followed by an intranasal boost rapidly induced robust mucosal IgA and systemic immunity in mice, with BCR-seq showing direct class switching of preexisting IgG+ B cells to IgA+ in draining nodes. In humans, the IN boost after prior IM vaccination elicited strong systemic IgA responses, supporting a strategy to enhance mucosal protection.

Key Findings

• IN boosting after IM priming markedly increased mucosal IgA and T/B cell responses in the upper respiratory tract of mice.
• BCR-seq indicated direct class switching from IgG+ to IgA+ B cells in draining lymph nodes after IN boost.
• Clinical studies showed robust systemic IgA increases in humans receiving an IN boost after IM vaccination.

Clinical Implications

Intranasal boosters after IM priming could augment mucosal immunity and may reduce infection and transmission risk, informing booster design for COVID-19 and other respiratory pathogens.

Limitations

• Human data focused on systemic IgA; direct measures of mucosal protection and clinical efficacy were not reported.
• Non-randomized human component with limited sample size details.

Future Directions

Randomized trials of IN boosters measuring mucosal antibodies and infection outcomes; optimization of dosing, intervals, and safety across age groups.