The Unexpected Impact of Vaccines on Secondary Bacterial Infections Following Influenza

Abstract

Influenza virus infections remain a significant health burden worldwide, despite available vaccines. Factors that contribute to this include a lack of broad coverage by current vaccines and continual emergence of novel virus strains. Further complicating matters, when influenza viruses infect a host, severe infections can develop when bacterial pathogens invade. Secondary bacterial infections (SBIs) contribute to a significant proportion of influenza-related mortality, with Streptococcus pneumoniae, Staphylococcus aureus, Streptococcus pyogenes, and Haemophilus influenzae as major coinfecting pathogens. Vaccines against bacterial pathogens can reduce coinfection incidence and severity, but few vaccines are available and those that are, may have decreased efficacy in influenza virus-infected hosts. While some studies indicate a benefit of vaccine-induced immunity in providing protection against SBIs, a comprehensive understanding is lacking. In this review, we discuss the current knowledge of viral and bacterial vaccine availability, the generation of protective immunity from these vaccines, and the effectiveness in limiting influenza-associated bacterial infections.

Keywords: influenza; protective immunity; secondary bacterial infections.

FIG. 1.

Timeline of available vaccines and influenza pandemics. Timeline of the major influenza virus pandemics from 1890 to 2017. Since the first isolation of an influenza virus in 1933, numerous vaccines have been developed and approved for use (white). Vaccines for pneumococcus (blue) and Hib (green), on the other hand, took nearly a century from the first isolation in 1881 and 1892, respectively.

FIG. 2.

Time course of influenza-bacterial coinfections and major causative agents. Influenza virus infection in unvaccinated individuals (dark gray) results in rapid viral growth before the virus peaks and the infection resolves. Bacteria often invade late in the infection, which can result in a rebound of viral loads (blue). In vaccinated individuals (light gray), viral loads are reduced and the infection length is shortened considerably, leaving little opportunity for bacterial invasion. Similarly, primary bacterial infections with S. pneumoniae, S. aureus, or S. pyogenes in vaccinated individuals (light gray) result in more mild infection compared to those that are unvaccinated (dark gray). When these pathogens invade during influenza (blue), bacteria grow rapidly with little immune control.