The potential of influenza HA-specific immunity in mitigating lethality of postinfluenza pneumococcal infections

Abstract

Influenza virus infections predispose an individual to secondary pneumococcal infections, which represent a serious public health concern. Matching influenza vaccination was demonstrated helpful in preventing post influenza bacterial infections and associated illnesses in humans. Yet, the impact of influenza hemagglutinin (HA)specific immunity alone in this dual-infection scenario remains elusive. In the present study, we assessed the protective effect of neutralizing and non neutralizing antihe magglutin in immunity in a BALB/c influenza-pneumococcus superinfection model. Our immunogens were insect cell expressed hemagglutinin Gag virus like particles that had been differentially treated for the inactivation of bioprocess related baculovirus impurities. We evaluated the potential of several formulations to restrain the primary infection with vaccine matched or mismatched influenza strains and secondary bacterial replication. In addition, we investigated the effect of anti HA immunity on the interferon status in mouse lungs prior to bacterial challenge. In our experimental setup, neutralizing anti HA immunity provided significant but incomplete protection from post influenza bacterial superinfection, despite effective control of viral replication. In view of this, it was surprising to observe a survival advantage with non neutralizing adaptive immunity when using a heterologous viral challenge strain. Our findings suggest that both neutralizing and non neutralizing antiHA immunity can reduce disease and mortality caused by postinfluenza pneumococcal infections.