Protective effect of nasal immunization of influenza virus hemagglutinin with recombinant cholera toxin B subunit as a mucosal adjuvant in mice.
To develop an efficient nasal influenza vaccine, influenza A and B virus HA with rCTB as a mucosal adjuvant were administered to mice intranasally. Serum anti-HA IgG and IgA antibody responses for both HA vaccines were significantly increased in the presence of rCTB. Higher HI and neutralizing antibody titers and higher mucosal IgA antibody responses in the respiratory tract were detected when rCTB was added than without rCTB. When mice were immunized with HA vaccine with or without rCTB and challenged by intranasal administration of mouse-adapted pathogenic influenza A virus, all mice immunized with HA plus rCTB survived for seven days without any inflammatory changes in the lungs, while not all the mice immunized with HA without rCTB survived, and all of them had lung consolidations. These results demonstrate that intranasal co-administration of rCTB as a mucosal adjuvant with influenza virus HA is necessary not only for the induction of systemic and mucosal HA antibodies, but also for the protection of mice from morbidity and mortality resulting from virus infection.
Isaka
Masanori
M
Department of Bacteriology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan. isaka@med.nagoya-cu.ac.jp
Zhao
Yanqiu
Y
Nobusawa
Eri
E
Nakajima
Setsuko
S
Nakajima
Katsuhisa
K
Yasuda
Yoko
Y
Matsui
Hideyuki
H
Hasegawa
Tadao
T
Maeyama
Jun-Ichi
J
Morokuma
Kazunori
K
Ohkuma
Kunio
K
Tochikubo
Kunio
K
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002772:Cholera Toxin / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000008:administration & dosage / Q000276:immunology*; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D012137:Respiratory System / Q000276:immunology; D016019:Survival Analysis
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007252:Influenza Vaccines; C493831:hemagglutinin HA1, influenza B virus; C483468:hemagglutinin, human influenza A virus; D002772:Cholera Toxin