UC Davis

BACKGROUND: Wildfires are increasingly common with wildfire smoke affecting millions globally, yet its impact on immune responses is poorly understood. Natural Killer (NK) cells play a role in mediating air pollutant effects and regulating vaccine immunity. OBJECTIVE: This real-world study, conducted on participants in the Pfizer BNT162b2 COVID-19 vaccine trial, studied the effects of wildfire smoke exposure on long-term vaccine effects. METHODS: We collected blood samples from 52 healthy, non-smoking participants (ages 26-83) before and 1 month after placebo or vaccine injections during heavy wildfire smoke events in Sacramento. The study included 28 vaccinated (Group 1) and 24 placebo-injected (Group 2) individuals, the latter vaccinated several months later, outside wildfire season. Blood samples from both Group 1 and 2 were also investigated 6 months after the second dose of vaccine. We analyzed intracellular cytokines, B and NK cell markers by flow cytometry, and serum immunoglobulin levels against common coronaviruses using multiplex assays. RESULTS: A robust S-RBD-specific IgG response observed 1 month post booster, declined variably 6 months later. Wildfire smoke acutely increased IL-13 expression by CD56bright NK cells. IL-13+CD56bright NK cells at the time of vaccination negatively correlated with anti-S-RBD IgG (r=-0.41, p<0.05) one month later. Total IgG levels on the other hand, positively correlated with the air quality index (AQI) measured during vaccination (r=0.96, p<0.01). Similarly to age (but not sex, BMI or race/ethnicity), the two-week AQI averages during vaccination showed a significant negative correlation with anti-S-RBD IgG levels 6 months later (r=-0.41, p<0.05). CONCLUSION: Wildfire smoke may lead to inappropriate immunoglobulin production and diminished vaccine immunity. Our novel findings highlight a previously unrecognized pathway involving NK-cell derived IL-13 and non-specific B-cell activation and underscore the significance of environmental exposures in shaping immunity.