Comparison of antiviral activity between IgA and IgG specific to influenza virus hemagglutinin: increased potential of IgA for heterosubtypic immunity.
Both IgA and IgG antibodies are known to play important roles in protection against influenza virus infection. While IgG is the major isotype induced systemically, IgA is predominant in mucosal tissues, including the upper respiratory tract. Although IgA antibodies are believed to have unique advantages in mucosal immunity, information on direct comparisons of the in vitro antiviral activities of IgA and IgG antibodies recognizing the same epitope is limited. In this study, we demonstrate differences in antiviral activities between these isotypes using monoclonal IgA and IgG antibodies obtained from hybridomas of the same origin. Polymeric IgA-producing hybridoma cells were successfully subcloned from those originally producing monoclonal antibody S139/1, a hemaggulutinin (HA)-specific IgG that was generated against an influenza A virus strain of the H3 subtype but had cross-neutralizing activities against the H1, H2, H13, and H16 subtypes. These monoclonal S139/1 IgA and IgG antibodies were assumed to recognize the same epitope and thus used to compare their antiviral activities. We found that both S139/1 IgA and IgG antibodies strongly bound to the homologous H3 virus in an enzyme-linked immunosorbent assay, and there were no significant differences in their hemagglutination-inhibiting and neutralizing activities against the H3 virus. In contrast, S139/1 IgA showed remarkably higher cross-binding to and antiviral activities against H1, H2, and H13 viruses than S139/1 IgG. It was also noted that S139/1 IgA, but not IgG, drastically suppressed the extracellular release of the viruses from infected cells. Electron microscopy revealed that S139/1 IgA deposited newly produced viral particles on the cell surface, most likely by tethering the particles. These results suggest that anti-HA IgA has greater potential to prevent influenza A virus infection than IgG antibodies, likely due to increased avidity conferred by its multivalency, and that this advantage may be particularly important for heterosubtypic immunity.
Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
Mieko
M
Muramatsu
Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
Reiko
R
Yoshida
Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
Ayaka
A
Yokoyama
Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
Hiroko
H
Miyamoto
Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
Masahiro
M
Kajihara
Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
Junki
J
Maruyama
Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
Naganori
N
Nao
Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
Rashid
R
Manzoor
Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan ; School of Veterinary Medicine, the University of Zambia, Lusaka, Zambia.
Ayato
A
Takada
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000998:Antiviral Agents / Q000276:immunology*; D004285:Dogs; D004591:Electrophoresis, Polyacrylamide Gel; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D006801:Humans; D007109:Immunity / Q000276:immunology*; D007070:Immunoglobulin A / Q000737:chemistry / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology*; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000276:immunology; D011485:Protein Binding; D013045:Species Specificity; D014771:Virion / Q000648:ultrastructure
D000914:Antibodies, Viral; D000998:Antiviral Agents; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007070:Immunoglobulin A; D007074:Immunoglobulin G