Role of IgA versus IgG in the control of influenza viral infection in the murine respiratory tract

The roles of IgG and secretory IgA in the protection of the respiratory tract (RT) against influenza infection remain unclear. Passive immunization with Ab doses resulting in serum IgG anti-influenza virus Ab titers far in excess of those observed in immune mice has compounded the problem. We compared the effects of i.v. anti-influenza virus IgG and i.v. anti-influenza virus polymeric IgA (pIgA) mAb administered in amounts designed to replicate murine convalescent serum or nasal Ab titers, respectively. A serum anti-influenza virus IgG titer 2.5 times the normal convalescent serum anti-influenza virus IgG titer was required for detectible Ab transudation into nasal secretions, and a serum IgG titer 7 times normal was needed to lower nasal viral shedding by 98%. Anti-influenza virus pIgA at a nasal Ab titer comparable to that seen in convalescent mice eliminated nasal viral shedding. The RT of influenza-infected pIgA- or IgG-protected mice were studied by scanning electron microscopy. Only pIgA was found to prevent virally induced pathology in the upper RT, suggesting that IgG did not prevent viral infection of the nose, but neutralized newly replicated virus after infection had been initiated. In contrast, IgG, but not pIgA, was found to prevent viral pathology in the murine lung. Our results help to resolve the controversy of IgA- vs IgG-mediated protection of the RT; both Abs are important, with plasma IgG Ab serving as the back-up for secretory IgA-mediated protection in the nasal compartment, and IgG being the dominant Ab in protection of the lung.