Poster Presentation BacPath 13: Molecular Analysis of Bacterial Pathogens Conference 2015

The pneumococcal whole cell vaccine reduces influenza-induced pneumococcal disease in the ears and lungs of co-infected infant mice (#204)

Jayne Manning 1 2 , Eileen M. Dunne 1 , Roy M. Robins-Browne 2 3 , Edward K. Mulholland 1 4 , Richard Malley 5 , Catherine Satzke 1 2 , Odilia L. Wijburg 2
  1. WRONG ONE, Murdoch Children's Research Institute, Parkville, Victoria, Australia
  2. Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
  3. Infectious Diseases and Microbiology, Murdoch Children's Research Institute, Parkville, Victoria, Australia
  4. London School of Hygiene and Tropical Medicine, London, United Kingdom
  5. Division of Infectious Diseases, Boston Children’s Hospital, Boston, USA

Streptococcus pneumoniae (the pneumococcus) is an important paediatric pathogen, causing a range of respiratory tract diseases including middle ear infection (otitis media, OM), and pneumonia. Over 90 pneumococcal serotypes exist, defined by their immunologically distinct capsular polysaccharide antigen. Current vaccines induce protection against only 10-13 serotypes. The pneumococcal whole cell vaccine (WCV) was developed to elicit serotype-independent protection and is currently undergoing phase II clinical trials. In mice, WCV reduces pneumococcal density in the nasopharynx via production of IL-17A by CD4+ Th17 cells and protects against invasive disease in an antibody-dependent manner. We investigated the effect of WCV on influenza-induced pneumococcal disease using an infant mouse model and two pneumococcal serotypes, 19F and 16F.  Six day old C57BL/6 mice were administered either WCV or adjuvant alone via subcutaneous injection. Mice were subsequently intranasally challenged with pneumococci at 12 days of age before infection with influenza A virus (Udorn/72 at 18 days old). Vaccine impact was determined at the peak of OM (6 days post-influenza) and during clearance (12 days post-influenza). WCV-mediated protection varied depending on the serotype tested: 19F density was significantly reduced in the ears, and 16F density was significantly reduced in the lungs of mice administered WCV compared to mice receiving adjuvant alone. WCV significantly reduced levels of both serotypes in the nasopharynx during clearance. Preliminary data suggest that WCV-induced protection against 19F in the ears may involve CD4+ T cells, since no reduction in 19F density was observed in vaccinated C57BL/6.GK1.5 mice that lack peripheral CD4+ T cells. We are currently investigating the immunological mechanisms of WCV-induced protection by correlating levels of protection with levels of antigen-specific antibodies and cytokine responses, as well as characterising inflammation in the ears and lungs.