Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2019

Direct interaction of whole inactivated influenza A and pneumococcal vaccines enhances influenza-specific immunity (#13)

Shannon C David 1 , Todd Norton 1 , Timona Tyllis 1 , Jasmine J Wilson 1 , Eve V Singleton 1 , Zoe Laan 1 , Justin B Davies 2 , Timothy R Hirst 1 , Iain Comerford 1 , Shaun McColl 1 , James Paton 1 , Mohammed Alsharifi 1
  1. Research Centre for Infectious Diseases, School of Biological Sciences, The University of Adelaide, Adelaide, SA, Australia
  2. Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW, Australia

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 previously reported our approach to develop a gamma-irradiated IAV vaccine (g-Flu) capable of inducing cross-protective immunity mediated by cross-reactive cytotoxic T cell responses (1). In addition, we recently reported the development of a serotype-independent pneumococcal vaccine using genetically modified non-capsulated bacteria inactivated by gamma-irradiation (g-PN) (2). Furthermore, we reported that co-administration of g-Flu with g-PN enhances pneumococcal-specific responses (3). Our recent study shows that mucosal co-administration of g-Flu and g-PN similarly augments IAV-specific immunity, particularly Tissue Resident Memory cell (TRM) responses in the lung (4). In addition, our in vitro analysis revealed that S. pneumoniae directly interacts with both g-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.

  1. Alsharifi, M., 2009. et al., Intranasal flu vaccine protective against seasonal and H5N1 avian influenza infections PLoS One, 4(4): p. e5336.
  2. Babb R, et al., 2016. Intranasal vaccination with ╬│-irradiated Streptococcus pneumoniae whole-cell vaccine provides serotype-independent protection mediated by B-cells and innate IL-17 responses. Clinical Science (Lond), 130(9):697-710.
  3. Babb, R., et al., 2017. Enhanced protective responses to a serotype-independent pneumococcal vaccine when combined with an inactivated influenza vaccine. Clin Sci (Lond), 131(2): p. 169-180
  4. David SC, et al., 2019. Direct interaction of whole inactivated influenza A and pneumococcal vaccines enhances influenza-specific immunity. Nature Microbiology- in press