Protection against influenza virus infection in polymeric Ig receptor knockout mice immunized intranasally with adjuvant-combined vaccines.
The role of secretory IgA in conferring cross-protective immunity was examined in polymeric (p)IgR knockout (KO) mice immunized intranasally with different inactivated vaccines prepared from A/PR/8/34 (H1N1), A/Yamagata/120/86 (H1N1), A/Beijing/262/95 (H1N1), and B/Ibaraki/2/85 viruses and infected with the A/PR/8/34 virus in the upper respiratory tract (RT)-restricting volume. In wild-type mice, immunization with A/PR/8/34 or its variant (A/Yamagata/120/86 and A/Beijing/262/95) vaccines conferred complete protection or partial cross-protection against infection, while the B-type virus vaccine failed to provide protection. The protection or cross-protection was accompanied by an increase in the nasal A/PR/8/34 hemagglutinin-reactive IgA concentration, which was estimated to be >30 times the serum IgA concentration and much higher than the nasal IgG concentration. In contrast, the blockade of transepithelial transport of dimeric IgA in pIgR-KO mice reduced the degree of protection or cross-protection, in parallel with the marked increase in serum IgA concentration and the decrease in nasal IgA concentration (about 20 and 0.3 times those in wild-type mice, respectively). The degree of the reduction of protection or cross-protection was moderately reversed by the low but non-negligible level of nasal IgA, transudates from the accumulated serum IgA. These results, together with the absence of the IgA-dependent cross-protection in the lower RT and the unaltered level of nasal or serum IgG in wild-type and pIgR-KO mice, confirm that the actively secreted IgA plays an important role in cross-protection against variant virus infection in the upper RT, which cannot be substituted by serum IgG.
Asahi
Yasuko
Y
Department of Pathology, National Institute of Infectious Diseases, Yakult Central Institute for Microbiological Research, and Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Yoshikawa
Tomoki
T
Watanabe
Izumi
I
Iwasaki
Takuya
T
Hasegawa
Hideki
H
Sato
Yuko
Y
Shimada
Shin-ichiro
S
Nanno
Masanobu
M
Matsuoka
Yoshiaki
Y
Ohwaki
Makoto
M
Iwakura
Yoichiro
Y
Suzuki
Yujiro
Y
Aizawa
Chikara
C
Sata
Tetutaro
T
Kurata
Takeshi
T
Tamura
Shin-ichi
S
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000737:chemistry; D002772:Cholera Toxin / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000008:administration & dosage / Q000276:immunology; D007117:Immunization, Secondary; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000737:chemistry; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000737:chemistry; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000235:genetics* / Q000276:immunology* / Q000517:prevention & control; D019056:Receptors, Polymeric Immunoglobulin / Q000172:deficiency* / Q000235:genetics*; D012141:Respiratory Tract Infections / Q000276:immunology / Q000517:prevention & control; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000276:immunology
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D019056:Receptors, Polymeric Immunoglobulin; D017778:Vaccines, Combined; D002772:Cholera Toxin