The upper respiratory tract is continuously exposed to a vast array of potentially pathogenic viruses and bacteria. Influenza A virus (IAV) has particular synergism with the commensal bacterium Streptococcus pneumoniae in this niche, and co-infection exacerbates pathogenicity and causes significant mortality. However, it is not known whether this synergism is associated with a direct interaction between the two pathogens. We have previously reported that co-administration of a whole-inactivated IAV vaccine (γ-Flu) with a whole-inactivated pneumococcal vaccine (γ-PN) enhances pneumococcal-specific responses. In this study, we show that mucosal co-administration of γ-Flu and γ-PN similarly augments IAV-specific immunity, particularly tissue-resident memory cell responses in the lung. In addition, our in vitro analysis revealed that S. pneumoniae directly interacts with both γ-Flu and with live IAV, facilitating increased uptake by macrophages as well as increased infection of epithelial cells by IAV. These observations provide an additional explanation for the synergistic pathogenicity of IAV and S. pneumoniae, as well as heralding the prospect of exploiting the phenomenon to develop better vaccine strategies for both pathogens.
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The data that support the findings of this study are available from the corresponding author upon request.
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The authors thank Adelaide University Microscopy (Adelaide, Australia) for assistance in sample preparation and operation of the FEI Tecnai G2 Spirit TEM. We also acknowledge the following funding sources supporting this research: an Australian Institute of Nuclear Science and Engineering (AINSE) Research Award (ALNGRA15517; to M.A.); an Australian Postgraduate Award and Gamma Vaccines Pty Ltd research sponsorship (to S.C.D.); and a National Health and Medical Research Council Senior Principal Research Fellowship (awarded to J.C.P.).
M.A. is head of the vaccine research group at the University of Adelaide and the Chief Scientific Officer of Gamma Vaccines Pty Ltd and Director of GPN Vaccines Pty Ltd, J.C.P. is a Director of GPN Vaccines Pty Ltd, and T.R.H. is the Executive Chairman of Gamma Vaccines Pty Ltd and GPN Vaccines Pty Ltd. This does not alter adherence to policies on sharing data and materials. Both Gamma Vaccines Pty Ltd and GPN Vaccines Pty Ltd have no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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David, S.C., Norton, T., Tyllis, T. et al. Direct interaction of whole-inactivated influenza A and pneumococcal vaccines enhances influenza-specific immunity. Nat Microbiol 4, 1316–1327 (2019). https://doi.org/10.1038/s41564-019-0443-4
Current Opinion in Virology (2019)
Nature Microbiology (2019)
Nature Microbiology (2019)