Protection Against Influenza Virus Infection in Polymeric Ig Receptor Knockout Mice Immunized Intranasally with Adjuvant-Combined Vaccines

• Published in: The Journal of immunology (1950) 2002-03, Vol.168 (6), p.2930-2938
• Main Authors: Asahi, Yasuko, Yoshikawa, Tomoki, Watanabe, Izumi, Iwasaki, Takuya, Hasegawa, Hideki, Sato, Yuko, Shimada, Shin-ichiro, Nanno, Masanobu, Matsuoka, Yoshiaki, Ohwaki, Makoto, Iwakura, Yoichiro, Suzuki, Yujiro, Aizawa, Chikara, Sata, Tetutaro, Kurata, Takeshi, Tamura, Shin-ichi
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - administration & dosage; Administration, Intranasal; AFc receptors; Animals; Antibodies, Viral - biosynthesis; Antibodies, Viral - chemistry; Cholera Toxin - administration & dosage; Cholera Toxin - immunology; Fc receptors; Female; Hemagglutinin Glycoproteins, Influenza Virus - administration & dosage; Hemagglutinin Glycoproteins, Influenza Virus - immunology; Immunization, Secondary; Immunoglobulin A - biosynthesis; Immunoglobulin A - chemistry; Immunoglobulin G - biosynthesis; Immunoglobulin G - chemistry; Influenza A virus - immunology; Influenza Vaccines - administration & dosage; Influenza Vaccines - immunology; Influenza virus; Male; Mice; Mice, Inbred BALB C; Mice, Knockout; Mice, Transgenic; Orthomyxoviridae Infections - genetics; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - prevention & control; Receptors, Polymeric Immunoglobulin - deficiency; Receptors, Polymeric Immunoglobulin - genetics; Respiratory Tract Infections - immunology; Respiratory Tract Infections - prevention & control; Vaccines, Combined - administration & dosage; Vaccines, Combined - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.168.6.2930

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.