Influenza vaccines to control influenza-associated bacterial infection: where do we stand?

Abstract

Influenza A virus is a pathogen that is feared for its capacity to cause pandemics. In this review, we illustrate the clinical evidence which support the theory that bacterial co-infection is a considerable risk factor for exacerbated disease during pandemic and seasonal influenza, including infection with influenza B viruses. We provide an overview of the multiple and diverse mechanisms that help explain how influenza creates an opportunity for replication of secondary bacterial infections. Influenza vaccines and pneumococcal vaccines are widely used and often in overlapping target groups. We summarize the evidence for a protective effect of influenza immunization against bacterial infections, and vice versa of pneumococcal vaccines against influenza-associated pneumonia and lethality. It is important that future implementation of broadly protective influenza vaccines also takes into account protection against secondary bacterial infection.

Keywords:

• influenza virus
• pandemic
• S. pneumoniae
• secondary bacterial infection

Financial & competing interests disclosure

Research on influenza in the group of Saelens is supported by a Research Collaboration with Sanofi Pasteur, FP7 Marie Curie Initial Training Network VACTRAIN, FP7 project FLUNIVAC (project number 602604), IUAP BELVIR project p7/45, FWO Research Project G052412N and Ghent University Special Research Grant BOF12/GOA/014, VIB. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Humans continuously live in close contact with a plethora of bacterial and viral species, requiring a stable balance between tolerance and immunity.

• Historical and scientific data underscore the ability of influenza viruses to grant certain bacterial species, such as Streptococcus pneumoniae and Staphylococcus aureus, the power to colonize the respiratory tract, causing severe pneumonia.

• The incidence of bacterial co-infection is drastically increased during influenza pandemics, providing a link with influenza virulence and lack of pre-existing immunity to the circulating influenza strains.

• Complicated pneumonia due to co-infection during seasonal influenza is predominant in adults older than 65 and in children less than 5 years of age; nevertheless, young adults are also at risk during pandemic influenza.

• Co-infection of bacteria and influenza is not restricted to influenza A only, also influenza B has the potential to cause significant excess morbidity and mortality due to bacterial superinfection.

• Influenza virus infection can directly create a niche for bacterial pathogens, by disrupting the epithelial barrier of the respiratory system.

• Immune silencing effects induced by influenza virus infection affects alveolar macrophage function, and induction of type I interferon further endows bacteria the ability to colonize the respiratory tract.

• By limiting primary viral infection and downstream immune responses, influenza vaccines have the ability to decrease secondary bacterial infections.

• There is some evidence that pneumococcal vaccination can reduce influenza-associated hospitalization by directly targeting the bacterial pathogens.

Notes