Effect of a pneumococcal whole cell vaccine on influenza A-induced pneumococcal otitis media in infant mice.
Vaccine
; 37(26): 3495-3504, 2019 06 06.
Article
in En
| MEDLINE
| ID: mdl-31103366
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 6â¯days of age, infected with pneumococci (EF3030 [serotype 19F] or PMP1106 [16F]) at 12â¯days of age, and given influenza A virus (A/Udorn/72/307 [H3N2], IAV) at 18â¯days of age to induce pneumococcal OM. Pneumococcal density in middle ear and nasopharyngeal tissues was determined 6 and 12â¯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 6â¯days post-viral infection (pâ¯=â¯0.022), and the density of both isolates in the nasopharynx at 12â¯days post-viral infection (EF3030, pâ¯=â¯0.035; PMP1106, pâ¯=â¯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 (pâ¯=â¯0.35) nor in wild-type mice given anti-CD4 monoclonal antibody before and after IAV inoculation (pâ¯=â¯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 (pâ¯=â¯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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Otitis Media
/
Pneumococcal Infections
/
Orthomyxoviridae Infections
/
Pneumococcal Vaccines
/
Influenza A Virus, H3N2 Subtype
Limits:
Animals
Language:
En
Journal:
Vaccine
Year:
2019
Document type:
Article
Affiliation country:
Australia