title: Protection against influenza virus infection by intranasal administration of hemagglutinin vaccine with chitin microparticles as an adjuvant.
abstract: Chitin in the form of microparticles (chitin microparticles, CMP) has been demonstrated to be a potent stimulator of macrophages, promoting T-helper-1 (Th1) activation and cytokine response. In order to examine the mucosal adjuvant effect of CMP co-administered with influenza hemagglutinin (HA) vaccine against influenza infection, CMP were intranasally co-administered with influenza HA vaccine prepared from PR8 (H1N1) virus. Inoculation of the vaccine with CMP induced primary and secondary anti-HA IgA responses in the nasal wash and anti-HA IgG responses in the serum, which were significantly higher than those of nasal vaccination without CMP, and provided a complete protection against a homologous influenza virus challenge in the nasal infection influenza model. In addition, CMP-based immunization using A/Yamagata (H1N1) and A/Guizhou (H3N2) induced PR8 HA-reactive IgA in the nasal washes and specific-IgG in the serum. The immunization with A/Yamagata and CMP resulted in complete protection against a PR8 (H1N1) challenge in A/Yamagata (H1N1)-vaccinated mice, while that with A/Guizhou (H3N2) and CMP exhibited a 100-fold reduction of nasal virus titer, demonstrating the cross-protective effect of CMP and influenza vaccine. It is suggested that CMP provide a safe and effective adjuvant for nasal vaccination with inactivated influenza vaccine.
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan. hasegawa@nih.go.jp
authors.forename: Hideki
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ichinohe
authors.forename: Peter
authors.initials: P
authors.lastname: Strong
authors.forename: Izumi
authors.initials: I
authors.lastname: Watanabe
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ito
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Tamura
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Takahashi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Sawa
authors.forename: Joe
authors.initials: J
authors.lastname: Chiba
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kurata
authors.forename: Tetsutaro
authors.initials: T
authors.lastname: Sata
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000494:pharmacology; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D002686:Chitin / Q000008:administration & dosage* / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009666:Nose / Q000821:virology; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D014611:Vaccination / Q000379:methods
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D002686:Chitin