Dual pathogen attack

According to estimates, around 50 million people died from the Spanish flu that broke out in 1918. This pandemic was triggered by a highly infectious strain of the influenza virus. Based on historical and clinical data, we know today that in a large proportion of cases the cause of death was not the viral disease itself, but pneumonia as a result of bacterial infection. Such secondary or superinfections develop on the hotbed of a previous viral infection and are still reason for concern even in the era of antibiotics. Scientists estimate that about a quarter of those who died in the 2009 influenza pandemic (popularly known as “swine flu”), had a bacterial co-infection. Researchers at the Vienna University of Natural Resources and Applied Life Sciences (BOKU) have now been able to show that an influenza vaccination also provides a protective shield against secondary bacterial infections. A research group led by Reingard Grabherr and principal investigator Miriam Klausberger addressed the issue in a project entitled “A VLP approach to combat post-influenza bacterial infections”. The group’s research relied on a promising state-of-the-art vaccine format.

Viruses make it easier to get started

“An influenza infection creates conditions in the body that make it easier for bacteria to get a foothold,” explains Miriam Klausberger. The effect is particularly strong in the first three to seven days after the viral infection. In this time window, even a low dose of bacteria can trigger a severe infection that would otherwise be harmless. A weakened immune system is not the only explanation, however. “After viral infection, the immune response misses important components. Moreover, in order to combat the virus the immune system activates components that are counterproductive in the face of bacterial infection,” notes Klausberger. These components include messenger substances of the immune system, such as type I (α/β) and type II (γ) interferon. They provide protection against viral infections but impair the recruitment and functioning of certain immune cells that are necessary to combat bacterial infection effectively.

Secondary bacterial infections are known not only from influenza but also from rhinoviruses, respiratory syncytial virus (RSV) or SARS-CoV-2. “When viruses multiply in the respiratory tract, they damage the surface of the outer cell layer,” Klausberger describes. “This makes it easier for bacteria to adhere to the mucosa and multiply.” In the influenza pandemics mentioned at the beginning, it was in particular the pathogens Staphylococcus aureus and Streptococcus pneumoniae in that took advantage of the viral leg-up. Both bacteria frequently colonize the human respiratory tract under normal circumstances without causing illness. S. pneumoniae, for example, can be detected in one out of two children up to the age of two. “Knowing that such bacteria are already present means that an influenza infection is an even greater potential hazard,” Klausberger warns.

How effective is vaccine protection?

The idea underlying Klausberger’s project is simple: “We know that an influenza infection prepares the ground for bacterial complications. It may therefore be beneficial to prevent the viral infection through vaccination.” In order to explore this hypothesis, BOKU researchers cooperated with the Moscow-based Mechnikov Research Institute for Vaccines and Sera. The Austrian researchers produced an influenza vaccine based on “virus-like particles” (VLPs). At the Russian institute these VLPs were used to immunize mice for the planned series of experiments.

“VLPs are a phenomenon that occurs naturally in many viruses,” Klausberger explains. “They are defective particles that are produced during virus replication.” While outwardly indistinguishable from their infectious counterparts, they cannot replicate because they lack the necessary genetic material. “This makes VLPs a relatively safe and very effective vaccine format.”