BACKGROUND: Endotoxin is a ubiquitous and potent proinflammatory agent. Previous limited studies suggest that it is pres-ent in allergen vaccines and that this could affect the safety and efficacy of allergen immunotherapy. The endotoxin content of standardized allergen vaccines is unknown. OBJECTIVE: The purpose of this study was to quantify the amount of endotoxin contained in standardized allergen vaccines. METHODS: The endotoxin content of 14 allergen vaccines was measured by using the Limulus amebocyte lysate (LAL) gel-clot assay. To account for (1,3)-beta-d-glucan and protease interference, vaccines were selectively depleted of endotoxin and then retested with the gel-clot assay. Proteases were also heat-inactivated in selected vaccines. Fifty-eight lots of vaccines were tested, including at least two manufacturers per vaccine. RESULTS: The endotoxin content of the 58 vaccines ranged from undetectable to 34,000 EU/mL. Cat pelt (12,735 EU/mL; range, 5177 to 33,805) had significantly more endotoxin activity than cat hair (2883 EU/mL; range, 1 to 16,962), and Dermatophagoides farinae extracts (4619 EU/mL; range, 849 to 8485) had more than Dermatophagoides pteronyssinus (11 EU/mL; range, 1 to 34). Grass (160 EU/mL; range, 3 to 1561) and ragweed pollen (341 EU/mL; range, 8 to 1697) vaccines contained less endotoxin. (1,3)-beta-d-glucan interference was significant (>10%) only in three ragweed vaccines and two grass vaccines. Heat inactivation had no effect. There were considerable differences in endotoxin content of the same vaccines made by different manufacturers. CONCLUSIONS: The endotoxin content of standardized allergen vaccines is extremely variable. Interference by proteases and (1,3)-beta-d-glucans is minimal. The effects of the high levels of endotoxin in some vaccines on the immunomodulatory changes associated with allergen immunotherapy require further study.
BACKGROUND: Endotoxin is a ubiquitous and potent proinflammatory agent. Previous limited studies suggest that it is pres-ent in allergen vaccines and that this could affect the safety and efficacy of allergen immunotherapy. The endotoxin content of standardized allergen vaccines is unknown. OBJECTIVE: The purpose of this study was to quantify the amount of endotoxin contained in standardized allergen vaccines. METHODS: The endotoxin content of 14 allergen vaccines was measured by using the Limulus amebocyte lysate (LAL) gel-clot assay. To account for (1,3)-beta-d-glucan and protease interference, vaccines were selectively depleted of endotoxin and then retested with the gel-clot assay. Proteases were also heat-inactivated in selected vaccines. Fifty-eight lots of vaccines were tested, including at least two manufacturers per vaccine. RESULTS: The endotoxin content of the 58 vaccines ranged from undetectable to 34,000 EU/mL. Cat pelt (12,735 EU/mL; range, 5177 to 33,805) had significantly more endotoxin activity than cat hair (2883 EU/mL; range, 1 to 16,962), and Dermatophagoides farinae extracts (4619 EU/mL; range, 849 to 8485) had more than Dermatophagoides pteronyssinus (11 EU/mL; range, 1 to 34). Grass (160 EU/mL; range, 3 to 1561) and ragweed pollen (341 EU/mL; range, 8 to 1697) vaccines contained less endotoxin. (1,3)-beta-d-glucan interference was significant (>10%) only in three ragweed vaccines and two grass vaccines. Heat inactivation had no effect. There were considerable differences in endotoxin content of the same vaccines made by different manufacturers. CONCLUSIONS: The endotoxin content of standardized allergen vaccines is extremely variable. Interference by proteases and (1,3)-beta-d-glucans is minimal. The effects of the high levels of endotoxin in some vaccines on the immunomodulatory changes associated with allergen immunotherapy require further study.
Authors: Joao G Magalhaes; Stephen J Rubino; Leonardo H Travassos; Lionel Le Bourhis; Wei Duan; Gernot Sellge; Kaoru Geddes; Karou Geddes; Colin Reardon; Matthias Lechmann; Leticia A Carneiro; Thirumahal Selvanantham; Jorg H Fritz; Betsy C Taylor; David Artis; Tak Wah Mak; Michael R Comeau; Michael Croft; Stephen E Girardin; Dana J Philpott Journal: Proc Natl Acad Sci U S A Date: 2011-08-19 Impact factor: 11.205
Authors: Anna H Nowak-Wegrzyn; Ramon Bencharitiwong; John Schwarz; Gloria David; Peyton Eggleston; Peter J Gergen; Andrew H Liu; Jacqueline A Pongracic; Sampson Sarpong; Hugh A Sampson Journal: J Allergy Clin Immunol Date: 2009-04 Impact factor: 10.793