Mutant Escherichia coli heat-labile enterotoxin [LT(R192G)] enhances protective humoral and cellular immune responses to orally administered inactivated influenza vaccine.
Influenza vaccines capable of inducing both systemic and mucosal antibody responses are highly desirable. Optimal induction of mucosal IgA is accomplished by mucosal delivery of vaccine. Mucosal adjuvants may improve the immunogenicity and efficacy of vaccines delivered by this route. Here, we compare the adjuvant activities of a mutant of heat-labile enterotoxin from Escherichia coli [LT(R192G)] with those of the wildtype LT (wtLT) for oral vaccination with inactivated influenza vaccine in BALB/c mice. Compared with administration of oral influenza vaccine alone, co-administration of vaccine with LT(R192G) provided enhanced protection from infection in the upper and lower respiratory tract equivalent to and at similar doses as that obtained with wtLT. Likewise, LT(R192G) augmented virus-specific IgG and IgA responses in serum, lung and nasal washes and the numbers of virus-specific antibody-forming cells in spleen, lung and Peyer's patches in a manner comparable to wtLT. Virus-specific splenic CD4(+) cells from mice administered oral vaccine with either adjuvant produced a mixed Th1- and Th2-type cytokine response pattern. Taken together, these results indicate that LT(R192G), like wtLT, is a potent adjuvant for oral vaccination of mice with influenza vaccine.
Lu
Xiuhua
X
Influenza Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, USA.
Clements
J D
JD
Katz
Jacqueline M
JM
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D001427:Bacterial Toxins / Q000494:pharmacology*; D002772:Cholera Toxin / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004768:Enterotoxins / Q000494:pharmacology*; D029968:Escherichia coli Proteins; D005260:Female; D007070:Immunoglobulin A / Q000096:biosynthesis; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D015164:Vaccines, Inactivated / Q000276:immunology
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D001427:Bacterial Toxins; D016207:Cytokines; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007070:Immunoglobulin A; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated; D002772:Cholera Toxin; C027538:heat-labile enterotoxin, E coli