title: Potential risk of repeated nasal vaccination that induces allergic reaction with mucosal IgE and airway eosinophilic infiltration in cynomolgus macaques infected with H5N1 highly pathogenic avian influenza virus.
abstract: The efficacy and detrimental effect of mucosal vaccination with an inactivated influenza vaccine were examined in a macaque model by intranasal administration with small amounts of inactivated whole virus particles and challenge by a human-derived H5N1 highly pathogenic avian influenza virus infection. Repeated nasal inoculation with the whole particle vaccine of an inactivated virus, A/duck/Hokkaido/Vac-3/2007 (H5N1) (Vac-3), induced antigen-specific IgA and IgG antibody production in nasal swabs and plasma. Vac-3-specific IgE production was also found in the nasal swabs. Nasal vaccination with Vac-3 induced broader cross-clade neutralization activity than did subcutaneous vaccination. After challenge infection, repeated nasal vaccination almost completely prevented the propagation of virus in the upper and lower airways and protected cynomolgus macaques from viral pneumonia by induction of IgA-producing B cells in the lungs. On the other hand, eosinophil clusters were observed in the lungs of vaccinated macaques. Although Vac-3-specific IgE antibody and IL-13 levels were decreased after infection compared to those before infection and no anaphylaxis in vaccinated macaques was detected after challenge infection, our results suggest that we have to pay attention to potential allergic responses at repeated nasal vaccination, especially in people who have an airway allergy.
authors.affiliation: Division of Pathology and Disease Regulation, Department of Pathology, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Misako
authors.initials: M
authors.lastname: Nakayama
authors.affiliation: Division of Pathology and Disease Regulation, Department of Pathology, Shiga University of Medical Science, Otsu, Japan. Electronic address: yasushii@belle.shiga-med.ac.jp.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Itoh
authors.affiliation: Division of Pathology and Disease Regulation, Department of Pathology, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Shichinohe
authors.affiliation: Division of Pathology and Disease Regulation, Department of Pathology, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Rumi
authors.initials: R
authors.lastname: Nakabayashi
authors.affiliation: Division of Pathology and Disease Regulation, Department of Pathology, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Hirohito
authors.initials: H
authors.lastname: Ishigaki
authors.affiliation: Laboratory of Microbiology, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan; Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sakoda
authors.affiliation: National Institute of Hygiene and Epidemiology, Hanoi, Viet Nam.
authors.forename: Quynh Mai
authors.initials: QM
authors.lastname: Le
authors.affiliation: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan; Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI, United States of America.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
authors.affiliation: Laboratory of Microbiology, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan; Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan; Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kida
authors.affiliation: Division of Pathology and Disease Regulation, Department of Pathology, Shiga University of Medical Science, Otsu, Japan; Research Center for Animal Life Science, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Ogasawara
mesh_terms: D000281:Administration, Intranasal / Q000009:adverse effects*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000096:biosynthesis*; D000914:Antibodies, Viral / Q000096:biosynthesis*; D004342:Drug Hypersensitivity / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology; D005260:Female; D007070:Immunoglobulin A / Q000096:biosynthesis; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage*; D008252:Macaca fascicularis / Q000276:immunology / Q000821:virology; D009297:Nasal Mucosa / Q000187:drug effects / Q000276:immunology; D020556:Neutrophil Infiltration / Q000187:drug effects; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D014611:Vaccination; D015164:Vaccines, Inactivated; D014771:Virion / Q000737:chemistry / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated; D007073:Immunoglobulin E
keywords: Eosinophil; H5N1 highly pathogenic avian influenza virus; IgE; Mucosal immunity; Nasal vaccination; Non-human primates