P-1979. Localized Nasal Mucosal SARS-CoV-2 Antibody Responses and Neutralization Potential based on Exposure History
Authors: Kim Minjun , Chwa Jason S , Shin Yunho , Lee Yesun , Cheng Wesley A , Jumarang Jaycee , Bender Jeffrey , Pannaraj Pia S 
Published: January 2025

Abstract

Background
SARS-CoV-2-specific mucosal antibodies inhibit viral replication and infection within the upper respiratory tract. We investigated nasal secretory IgA (SIgA) induction differences by exposure history and protection against subsequent infection.
Visual schematic of exposure groups.

Methods
Between June 2020 and February 2024, nasopharyngeal swab (NPS) samples were collected 14-89 days following recent infection or vaccination. SARS-CoV-2-specific nasal SIgA adjusted for total IgA (SIgAadj) and nasal neutralization activity were measured using ELISA and a surrogate virus neutralization test kit, respectively. Subsequent infection risk was compared in participants stratified by mucosal antibody levels using a Cox proportional hazards model.
Figure 2
SARS-CoV-2 specific nasal secretory IgA adjusted for total IgA (SIgAadj) by exposure group compared using Wilcoxon rank sum tests.

Results
NPS were collected from participants with SARS-CoV-2 infection only (n=94), vaccination only (n=94), infection then vaccination (n=51), and breakthrough infection (n=94) (Fig 1). Vaccinated individuals received 3 doses of BNT162b2 (n=199, 82.7%) or mRNA-1273 (n=40, 17.3%). The mean age was 28.2 years (range 0.4-75.1), and 197 (59.2%) were female. Individuals with breakthrough infection after vaccination mounted the highest nasal SIgAadj response compared to those with infection-only (median 10.8 vs. 1.3 AU/mL, P &lt; 0.001), vaccination-only (median 0.2 AU/mL, P&lt; 0.001), or prior infection then vaccinated (median 3.2 AU/mL, P = 0.016) (Fig 2). Neutralization activity correlated with nasal SIgAadj (ρ = 0.48, P &lt; 0.001). If vaccination was the most recent exposure, SIgA did not correlate with serum IgG (ρ = 0.08, P = 0.3). Forty new SARS-CoV-2 infections occurred during the 12-month follow-up period (Fig 3). In a multivariable analysis to account for age, gender, and serum IgG, participants with the lowest quartile of nasal SIgAadj levels had 5.8 times higher odds of infection than those with the higher three quartiles of nasal SIgAadj levels within 3 months (P = 0.005) (Table 1).
Figure 3
Kaplan-Meier survival curves of time to subsequent SARS-CoV-2 infection in participants stratified by SARS-CoV-2-specific nasal adjusted SIgA upper 75% quantiles (high) vs. lower 25% quartile (low) over 12 months. P = 0.004 for 0-3 months and P = 0.029 for 0-12 months.

Conclusion
Our data demonstrate the protective role of nasal SIgA in lowering SARS-CoV-2 infection risk. Hybrid immunity induced the most robust mucosal response, suggesting a mucosal vaccine boost following intramuscular priming may help maximize mucosal immunity to prevent infection and community transmission.
Predictors of subsequent infection within 0-3, 3-6, and 6-12 months using Cox proportional hazards regression model.

Disclosures
Pia S. Pannaraj, MD, MPH, AstraZeneca: Grant/Research Support|Pfizer: Grant/Research Support