title: Heterosubtypic antiviral activity of hemagglutinin-specific antibodies induced by intranasal immunization with inactivated influenza viruses in mice.
abstract: Influenza A virus subtypes are classified on the basis of the antigenicity of their envelope glycoproteins, hemagglutinin (HA; H1-H17) and neuraminidase. Since HA-specific neutralizing antibodies are predominantly specific for a single HA subtype, the contribution of antibodies to the heterosubtypic immunity is not fully understood. In this study, mice were immunized intranasally or subcutaneously with viruses having the H1, H3, H5, H7, H9, or H13 HA subtype, and cross-reactivities of induced IgG and IgA antibodies to recombinant HAs of the H1-H16 subtypes were analyzed. We found that both subcutaneous and intranasal immunizations induced antibody responses to multiple HAs of different subtypes, whereas IgA was not detected remarkably in mice immunized subcutaneously. Using serum, nasal wash, and trachea-lung wash samples of H9 virus-immunized mice, neutralizing activities of cross-reactive antibodies were then evaluated by plaque-reduction assays. As expected, no heterosubtypic neutralizing activity was detected by a standard neutralization test in which viruses were mixed with antibodies prior to inoculation into cultured cells. Interestingly, however, a remarkable reduction of plaque formation and extracellular release of the H12 virus, which was bound by the H9-induced cross-reactive antibodies, was observed when infected cells were subsequently cultured with the samples containing HA-specific cross-reactive IgA. This heterosubtypic plaque reduction was interfered when the samples were pretreated with anti-mouse IgA polyclonal serum. These results suggest that the majority of HA-specific cross-reactive IgG and IgA antibodies produced by immunization do not block cellular entry of viruses, but cross-reactive IgA may have the potential to inhibit viral egress from infected cells and thus to play a role in heterosubtypic immunity against influenza A viruses.
authors: Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
authors: Mieko
authors: M
authors: Muramatsu
authors: Reiko
authors: R
authors: Yoshida
authors: Hiroko
authors: H
authors: Miyamoto
authors: Daisuke
authors: D
authors: Tomabechi
authors: Masahiro
authors: M
authors: Kajihara
authors: Junki
authors: J
authors: Maruyama
authors: Takashi
authors: T
authors: Kimura
authors: Rashid
authors: R
authors: Manzoor
authors: Kimihito
authors: K
authors: Ito
authors: Ayato
authors: A
authors: Takada
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology; D004285:Dogs; D005260:Female; D057809:HEK293 Cells; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D006801:Humans; D007114:Immunization; D009980:Influenza A virus / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D007279:Injections, Subcutaneous; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000097:blood / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D010802:Phylogeny; D038301:Virus Inactivation
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D009439:Neuraminidase
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