Real-life observation of wildfire smoke-impaired COVID-19 vaccine immunity.

Abstract

Wildfires are increasingly common, with wildfire smoke affecting millions globally; yet, its impact on immune responses is poorly understood. This real-world study, conducted on participants in the Pfizer BNT162b2 coronavirus disease 2019 (COVID-19) vaccine trial, examined the effects of wildfire smoke exposure on long-term vaccine immunity. We recruited 52 healthy, nonsmoking individuals (aged 26-83 years) who were either vaccinated (group 1 [n = 28]) or injected with placebo (group 2 [n = 24]) during conditions of heavy wildfire smoke. The group 2 subjects underwent vaccination several months later, outside wildfire season. Blood was taken before and 1 month after the vaccine or placebo injections, as well as 6 months after vaccination. We analyzed levels of intracellular cytokines, B-cell, and natural killer (NK) cell markers by flow cytometry, as well as serum immunoglobulin levels against common coronaviruses by using multiplex assays. A robust spike receptor-binding domain (S-RBD)-specific IgG response was observed 1 month after booster and declined variably 6 months later. Wildfire smoke acutely increased IL-13 expression by CD56^bright NK cells at the time of vaccination; this increase negatively correlated with level of anti-S-RBD IgG (r = -0.41; P < .05). Total IgG levels positively correlated with the Air Quality Index measured during vaccination (r = 0.96; P < .01). Similarly to age (but not to sex, body mass index, or race/ethnicity), the 2-week Air Quality Index averages during vaccination showed a significant negative correlation with anti-S-RBD IgG levels 6 months later (r = -0.41; P < .05). Wildfire smoke may lead to inappropriate immunoglobulin production and diminished vaccine immunity. We highlight a previously unrecognized pathway involving NK cell-derived IL-13 and nonspecific B-cell activation and underscore the significance of environmental exposures in shaping immunity.