A VLP approach to combat postinfluenza bacterial infections
Abstract
Clinical and historical data underscore the ability of influenza viruses to ally with certain bacterial species and predispose the host for secondary bacterial infection. Bacterial pneumonia postinfluenza infection was identified as the major cause of mortality during the most devastating influenza pandemics in 1918/19 and 1957/58 with S.aureus and S.pneumoniae being the most commonly associated etiological agents. Vaccination is the best method to prevent infectious disease. There is, however, no S.aureus prophylaxis available and S.pneumoniae vaccines were shown to be largely ineffective. On top, the rise of multi-drug-resistant bacterial strains is alarming. Yet, it was shown that by limiting primary viral infection, influenza vaccines are able to decrease subsequent secondary bacterial infections, leaving influenza vaccines as only promising measure to prevent secondary bacterial complications. Low cross-reactivity of current influenza vaccines, however, still enables drifted influenza strains to cause disease and may prime patients for difficult-to-treat bacterial superinfections. Several viral and host key players have been identified to increase susceptibility of the host for postinfluenza secondary infection. The influenza neuraminidase was shown to increase bacterial adherence to epithelial tissues, by unmasking and up-regulating expression of cellular receptors. The viral proteins PB1-F2 and NS1 may suppress the host innate bacterial responses by modulating the host interferon response and dysregulating cytokine and chemokine secretion. Current influenza vaccines are standardized as per their hemagglutinin content and the amount of other viral proteins present is predefined by their natural abundance in the influenza virion. This leaves the influenza NA and (to an even higher degree) the NS1 largely underrepresented in current vaccines, whereas PB1-F2 is even absent. We aim to supplement/enrich a virus-like particle preparation based on the influenza HA and a non-influenza capsid protein with these antigens at different ratios compared to the HA. These preparations will be evaluated for their beneficial contribution in protective efficacy against S.aureus and S.pneumoniae infections after heterologous influenza infection; mimicking the situation of vaccine mismatch.
keywords VLP vaccine influenza virus secoundary infection secondary infection
Publikationen
Project staff
Miriam Klausberger
Dipl.-Ing. Miriam Klausberger Ph.D.
miriam.klausberger@boku.ac.at
Tel: +43 1 47654-79858, 79928
Project Leader
01.07.2018 - 31.05.2022
Maximilian Freudhofmaier
Maximilian Freudhofmaier
Tel: +43 1 47654-79928
Project Staff
01.01.2020 - 30.04.2020
BOKU partners
External partners
Federal State Budgetary Scientific Institution “ I.Mechnikov Research Institute for Vaccines and Sera”
none
partner