The Potential of Influenza HA-Specific Immunity in Mitigating Lethality of Postinfluenza Pneumococcal Infections

Abstract

: Influenza virus infections pre-dispose an individual to secondary pneumococcal infections, which represent a serious public health concern. Matching influenza vaccination was demonstrated helpful in preventing postinfluenza 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 anti-hemagglutinin 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 postinfluenza 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 anti-HA immunity can reduce disease and mortality caused by postinfluenza pneumococcal infections.

Increased efficacy of influenza virus vaccine candidate through display of recombinant neuraminidase on virus like particles

“…When adding NA to an existing vaccine, addition of extra adjuvants should be avoided, since increased reactogenicity could arise as a consequence. While soluble proteins often are inefficiently immunogenic when unadjuvanted, particle structures often induce immune response without the presence of adjuvanting agents ( 22 ).…”

“…Here, and based on previous work ( 22 – 24 ), we have generated VLPs in insect cells, that are based on self-assembly and budding of the human immunodeficiency virus 1 (HIV-1) gag protein, and display N2 NA on their surface. N2 was chosen because of the high diversity of H3N2 viruses in the human population and the resulting typically low vaccine effectiveness ( 25 ).…”

Live Influenza Vaccine Provides Early Protection against Homologous and Heterologous Influenza and May Prevent Post-Influenza Pneumococcal Infections in Mice

“…This leads to an increased proliferation of bacteria in the upper and lower respiratory tracts and increases the severity of bacterial complications, such as secondary bacterial pneumonia and otitis media [11]. In a mouse model of parenteral immunization with pseudoviruses containing HA of A/Puerto Rico/8/1934, it was shown that both vaccine-matching and non-matching HA antibodies may reduce morbidity and mortality due to post-influenza pneumococcal infections [12].…”

Immunoinformatics analysis and evaluation of recombinant chimeric triple antigen toxoid (r-HAB) against Staphylococcus aureus toxaemia in mouse model

“…Difficulties in developing prophylactic and therapeutic measures against S. aureus emerge from the fact that, organism possesses multiple arsenals of virulence and immune evasion factors, multiple manifestations of infections and our limited understanding of the intricacies of host–pathogen interactions (Fowler and Proctor 2014 ; Reddy et al 2017 ). Lack of protective licensed vaccine combined with dramatic increase of antibiotic-resistant strains in hospital and community at alarming rate has further added to treatment woes (Klausberger et al 2019 ).…”