Mucosal immunity to influenza without IgA: An IgA knockout mouse model

IgA knockout mice (IgA(-/-)) were generated by gene targeting and mere used to determine the role of IgA in protection against mucosal infection by in fluenza and the value of immunization for preferential induction of secreto ry IgA, Aerosol challenge of naive IgA(-/-) mice and their mild-type IgA(+/ +) littermates with sublethal and lethal doses of influenza virus resulted in similar levels of pulmonary virus infection and mortality, Intranasal an d i.p. immunization with influenza vaccine plus cholera toxin/cholera toxin B induced significant mucosal and serum influenza hemagglutinin-specific I gA Abs in IgA(+/+) (but not IgA(-/-)) mice as well as IgG and IgM Abs in bo th IgA(-/-) and IgA(+/+) mice; both exhibited similar levels of pulmonary a nd nasal virus replication and mortality following a lethal influenza virus challenge, Monoclonal anti-hemagglutinin IgG1, IgG2a, IgM, and polymeric I gA Abs were equally effective in preventing influenza virus infection in Ig A(-/-) mice, These results indicate that IgA is not required for prevention of influenza virus infection and disease, Indeed, while mucosal immunizati on for selective induction of IgA against influenza may constitute a useful approach for control of influenza and other respiratory viral infections, strategies that stimulate other Igs in addition may be more desirable.