ePoster Presentation 49th Annual Scientific Meeting of the Australian and New Zealand Society for Immunology 2021

Assessing the nonspecific effects of whole-cell DTP-containing vaccines in murine models of infection and asthma (#191)

Natalie Stevens 1 , Miriam A Lynn 1 , Todd Norton 1 , Feargal J Ryan 1 , David J Lynn 1
  1. SAHMRI, Adelaide, SA, Australia

Increasing evidence suggests that vaccines elicit nonspecific effects on morbidity and mortality unrelated to the targeted diseases. Live vaccines (e.g. BCG) are associated with beneficial nonspecific effects, while some inactivated vaccines (e.g. whole-cell DTP, or DTPw) have controversially been associated with increased all-cause mortality in populations with high infant mortality. We have recently shown that immunisation of mice with DTPw-containing vaccines induces “trained immunity”, an epigenetic and metabolic reprogramming of innate immune cells, compared to BCG-immunised mice. Whether DTPw-induced trained immunity alters responses to other infections or inflammatory challenges is currently unknown. To assess the impact of DTPw-containing vaccines on immune responses to subsequent challenges we assessed DTPw immunised mice in three different models of infection and inflammation, in comparison to BCG or mock immunised mice. These models included a cecal ligation puncture model of polymicrobial sepsis, an PR8 influenza challenge model, and a model of OVA-induced allergic asthma. While we observed increased proinflammatory cytokine responses and morbidity in DTPw-vaccinated mice in a non-lethal model of CLP sepsis, immunisation with DTPw-containing vaccine was not associated with increased morbidity or mortality in a polymicrobial sepsis survival model. Similarly, DTPw immunisation did not alter survival in an influenza challenge model. While DTPw vaccination did not lead to altered innate immune responses in the lung in an OVA-induced allergic asthma model, serum anti-OVA antibody responses were altered with DTPw mice exhibiting a lower OVA-specific IgE/IgG2a ratio compared to mock-immunised mice, suggesting a reduced propensity towards allergic antibody responses. Our data suggest that immunisation with DTPw-containing vaccines does not promote allergic disease or increased mortality from viral or bacterial infection in mice.