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Trivalent pneumococcal protein vaccine protects against experimental acute otitis media caused by Streptococcus pneumoniae in an infant murine model
- Source :
- Vaccine. 35:337-344
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- Background Currently licensed serotype-based pneumococcal vaccines are effective in preventing invasive pneumococcal diseases, but less effective in preventing non-bacteremic pneumonia and acute otitis media (AOM). We previously reported that a trivalent pneumococcal protein recombinant vaccine (PPrV) protected against pneumonia in a murine model. Here we evaluated PPrV protection against AOM in an infant murine model. Methods C57BL/6J mice were intramuscularly vaccinated at 1–3 weeks of age with monovalent pneumococcal histidine triad protein D (PhtD), or pneumococcal choline binding protein A (PcpA), or detoxified pneumolysin (PlyD1), or trivalent vaccine, and transtympanically challenged at 7–8 weeks of age with 1 × 10 2 CFU of pneumococcal strain BG7322 (6A) or 1 × 10 4 CFU of pneumococcal nontypeable strain 0702064 MEF. Serum IgG titers were determined by ELISA. At 24 and 48 h post infection (hpi), animals were sacrificed and middle ear fluid (MEF) samples were collected to determine pneumococcal CFUs . Results We found that vaccination of infant mice with monovalent and trivalent pneumococcal proteins elicited significant serum IgG antibody responses to corresponding component proteins. Vaccination with PhtD reduced BG7322 bacterial burdens in MEF at both 24 (p = 0.05) and 48 hpi (p = 0.16). Vaccination with PcpA significantly reduced the bacterial burdens in MEF at both 24 (p = 0.02) and 48 hpi (p = 0.004), and PlyD1 significantly reduced bacterial burden in MEF at 48 hpi (p = 0.02). Vaccination with trivalent PPrV (PhtD, PcpA and PlyD1) significantly reduced Spn burdens in MEF at both 24 (p = 0.001) and 48 hpi (p Spn strain. Vaccinated mice had significantly milder inflammatory cytokine levels (IL-1β, IL-6, TNF-α, MIP-2 and KC) in middle ears at 24 hpi (all p values Conclusion Trivalent PPrV confers protection against pneumococcal AOM in an infant murine model.
- Subjects :
- Male
0301 basic medicine
Serotype
Colony Count, Microbial
Ear, Middle
Enzyme-Linked Immunosorbent Assay
medicine.disease_cause
Injections, Intramuscular
Pneumococcal Infections
Microbiology
Pneumococcal Vaccines
03 medical and health sciences
0302 clinical medicine
Bacterial Proteins
Streptococcus pneumoniae
Animals
Medicine
030212 general & internal medicine
Interleukin 6
Vaccines, Synthetic
Pneumolysin
General Veterinary
General Immunology and Microbiology
biology
business.industry
Public Health, Environmental and Occupational Health
Exudates and Transudates
medicine.disease
Antibodies, Bacterial
Bacterial Load
Mice, Inbred C57BL
Vaccination
Disease Models, Animal
Otitis Media
Titer
Pneumonia
Treatment Outcome
030104 developmental biology
Infectious Diseases
Animals, Newborn
Immunization
Immunoglobulin G
Vaccines, Subunit
Immunology
biology.protein
Molecular Medicine
Female
business
Subjects
Details
- ISSN :
- 0264410X
- Volume :
- 35
- Database :
- OpenAIRE
- Journal :
- Vaccine
- Accession number :
- edsair.doi.dedup.....d2f7513ad4c1201c7cc315ce267827d5