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Vaccine. 2019 Jun 6;37(26):3495-3504. doi: 10.1016/j.vaccine.2019.03.013. Epub 2019 May 15.

Effect of a pneumococcal whole cell vaccine on influenza A-induced pneumococcal otitis media in infant mice.

Author information

1
Pneumococcal Research, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia; Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
2
Pneumococcal Research, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia; Department of Paediatrics, Royal Children's Hospital, The University of Melbourne, Melbourne, Victoria, Australia.
3
Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
4
TissuPath Pty. Ltd., Hawthorn, Victoria, Australia.
5
Department of Paediatrics, Royal Children's Hospital, The University of Melbourne, Melbourne, Victoria, Australia; Neurogenetics, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia.
6
Pneumococcal Research, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia; Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, United Kingdom.
7
Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia; Infectious Diseases, Murdoch Children's Research Institute, Parkville, VIC, Australia.
8
Division of Infectious Diseases, Boston Children's Hospital, Boston, United States.
9
Pneumococcal Research, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia; Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia; Department of Paediatrics, Royal Children's Hospital, The University of Melbourne, Melbourne, Victoria, Australia. Electronic address: catherine.satzke@mcri.edu.au.

Abstract

The pneumococcus remains a common cause of otitis media (OM) despite the widespread introduction of pneumococcal conjugate vaccines. In mice, a pneumococcal whole cell vaccine (WCV) induces serotype-independent protection against pneumococcal colonisation and invasive disease via TH17- and antibody-mediated immunity, respectively. We investigated the effect of WCV on influenza A-induced pneumococcal OM in an infant mouse model. C57BL/6 mice were immunised subcutaneously with a single dose of WCV or adjuvant at 6 days of age, infected with pneumococci (EF3030 [serotype 19F] or PMP1106 [16F]) at 12 days of age, and given influenza A virus (A/Udorn/72/307 [H3N2], IAV) at 18 days of age to induce pneumococcal OM. Pneumococcal density in middle ear and nasopharyngeal tissues was determined 6 and 12 days post-virus. Experiments were repeated in antibody (B6.μMT-/-)- and CD4+ T-cell-deficient mice to investigate the immune responses involved. A single dose of WCV did not prevent the development of pneumococcal OM, nor accelerate pneumococcal clearance compared with mice receiving adjuvant alone. However, WCV reduced the density of EF3030 in the middle ear at 6 days post-viral infection (p = 0.022), and the density of both isolates in the nasopharynx at 12 days post-viral infection (EF3030, p = 0.035; PMP1106, p = 0.011), compared with adjuvant alone. The reduction in density in the middle ear required antibodies and CD4+ T cells: WCV did not reduce EF3030 middle ear density in B6.μMT-/- mice (p = 0.35) nor in wild-type mice given anti-CD4 monoclonal antibody before and after IAV inoculation (p = 0.91); and WCV-immunised CD4+ T cell-deficient GK1.5 mice had higher levels of EF3030 in the middle ear than their adjuvant-immunised counterparts (p = 0.044). A single subcutaneous dose of WCV reduced pneumococcal density in the middle ears of co-infected mice in one of two strains tested, but did not prevent OM from occurring in this animal model.

KEYWORDS:

Influenza A virus; Mouse model; Otitis media; Pneumococcus; Streptococcus pneumoniae; Vaccine; Whole cell vaccine

PMID:
31103366
DOI:
10.1016/j.vaccine.2019.03.013
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