A study published in JCI Insight demonstrates that intranasal COVID-19 boosters can “reprogram” immunity from prior intramuscular vaccines, producing nasal antibodies more effective at neutralising Omicron variants than standard blood antibodies.
Current intramuscular vaccines effectively generate blood-based immunity and reduce severe disease, but offer limited protection in the nasal and throat cavities, the primary entry points for SARS-CoV-2. This helps explain breakthrough infections in vaccinated individuals.
Participants who had received inactivated whole-virus vaccines were given a two-dose intranasal booster (Ad5-S-Omicron vaccine). Purified nasal secretory IgA (sIgA) proved substantially more potent than blood-based IgG, with effectiveness ranging from 17-fold greater against the wild-type virus up to 813-fold greater against the XBB.1.5 variant.
The nasal booster triggered several immune mechanisms: reactivation of memory B cells from original injections, a shift from IgG to IgA antibody production, and upregulation of receptors directing immune cells to the nasal mucosa.
The study involved small subgroups (6 participants for paired antibody analyses, 8 for cytokine profiling), with detailed analyses largely derived from a single donor, limiting generalizability. Additionally, nasal sIgA levels declined 65% within three months, suggesting regular boosters may be needed to maintain protection. Clinical effectiveness and durability require confirmation in larger trials. The study evaluated immune responses rather than transmission outcomes.
Published in: JCI Insight (2026)
