Adjuvant activity of the heat-labile enterotoxin from enterotoxigenic Escherichia coli for oral administration of inactivated influenza virus vaccine.
Alternative strategies for vaccination against influenza that elicit both systemic antibody and mucosal IgA responses are needed to improve the efficacy in protection against infection. This study demonstrated that oral delivery of inactivated influenza vaccine with the heat-labile enterotoxin (LT) from enterotoxigenic Escherichia coli elicited the spectrum of humoral and cell-mediated responses in BALB/c mice critical for the protection and recovery from influenza virus infection. Coadministration of LT with oral influenza vaccine increased antiviral serum IgG and mucosal IgA responses compared with administration of oral influenza vaccine alone. Serum hemagglutination-inhibition and neutralizing antibodies were also augmented by LT. The adjuvant potentiated protection from infection with influenza A H3N2 viruses in mouse lower and upper respiratory tracts, enabling the use of lower doses of oral vaccine. Coadministration of LT with oral inactivated influenza vaccine induced influenza virus-specific proliferative T cells, interleukin-2 production, and major histocompatibility complex class I-restricted cytotoxic T cells.
Katz
J M
JM
Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
Lu
X
X
Young
S A
SA
Galphin
J C
JC
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000284:Administration, Oral; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D004768:Enterotoxins / Q000008:administration & dosage / Q000276:immunology*; D004926:Escherichia coli / Q000276:immunology*; D005260:Female; D006385:Hemagglutination Inhibition Tests; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007111:Immunity, Cellular; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000032:analysis / Q000276:immunology; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology; D007075:Immunoglobulin M / Q000032:analysis / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D009981:Influenza B virus / Q000276:immunology; D007376:Interleukin-2 / Q000378:metabolism; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000097:blood / Q000276:immunology* / Q000517:prevention & control*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D004768:Enterotoxins; D015395:Histocompatibility Antigens Class I; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007376:Interleukin-2; D015164:Vaccines, Inactivated