Association between tick-bite history and safety of gelatin-containing vaccines: Analysis of a large database of the United States

Alpha-gal syndrome (AGS) is an allergic reaction caused by sensitization to alpha-gal, a sugar molecule in gelatin-containing vaccines. Tick bites can induce alpha-gal IgE sensitization, as ticks inject alpha-gal through their saliva. However, there is no real-world data on the anaphylaxis rates associated with gelatin-containing vaccines in patients with tick bite history. We utilized TriNetX, a research network database, to analyze data in November 2024. The history of tick bites (i.e., the presence of a tick-bite history) was categorized into three groups: ehrlichiosis, tularemia, and bites from nonvenomous arthropods. Vaccines were classified into two categories: (1) gelatin-containing vaccines (live intranasal influenza [FluMist], varicella, measles/mumps/rubella [MMR], oral typhoid, rabies [RabAvert], and yellow fever vaccines [YF-VAX]) and (2) gelatin-free vaccines. Anaphylactic episodes were identified in patients with a history of tick bites who developed anaphylaxis within one day following vaccination. The anaphylaxis rates after receiving gelatin-containing vaccines were 0.06 %, 0.7 %, and 0.2 % in patients with ehrlichiosis, tularemia, and nonvenomous arthropod bites, respectively. In contrast, the anaphylaxis rates after receiving gelatin-free vaccines were 0.04 %, 0.0 %, and 0.1 % in patients with ehrlichiosis, tularemia, and nonvenomous arthropod bites, respectively. Among the gelatin-containing vaccines, live intranasal influenza and varicella vaccines posed a higher rate of anaphylaxis compared to other gelatin-containing vaccines. While tick bites are associated with AGS, a history of tick bites is not a contraindication for most gelatin-containing vaccines, including MMR, oral typhoid, rabies, and yellow fever vaccines. Further investigations are warranted to evaluate the safety of intranasal influenza and varicella vaccines in this population.