Protective efficacy of virus like particles (VLPs) containing the influenza HA and/or NA in a murine model of postinfluenza bacterial pneumonia

Abstract

An influenza virus infection primes the host for secondary bacterial infections. We previously have shown that immunity towards the influenza hemagglutinin (HA) alone reduces disease and mortality caused by pneumococcal infections after an influenza infections in mice. Whether this protective effect may be potentiated by supplementing the HA preparation with the influenza neuraminidase (NA) remains underexplored. To address this question, we employed HIV-1 Gag VLPs pseudo-typed with the influenza HA or NA from PR8 as platform to investigate immunity towards these to antigens, exclusively or in combination, in a lethal BALB/c mouse model of pneumococcal infection after vaccine-matched or -mismatched influenza virus challenge. A cocktail of vaccine-matched HA-Gag and NA-Gag VLPs fully protected from weight loss, mortality and viral replication and significantly reduced the bacterial burden in the lungs of infected animals. More importantly, immunization with this immunogen cocktail also protected 60% of animals from mortality associated with secondary bacterial infection using a heterologous H1N1 influenza virus and mice were significantly protected from weight loss and pulmonary pathogen replication in the absence of hemagglutination-inhibition and neuraminidase–inhibition antibodies. Our results indicate that influenza vaccination may profoundly influence the outcome of a sequential influenza-pneumococcal infection scenario even when the viral invader is antigenically distant to the vaccine strain. Work was supported by the RSF-FWF grant 18-45-05002 (FWF I 3490-B30)