Trivalent pneumococcal protein vaccine protects against experimental acute otitis media caused by Streptococcus pneumoniae in an infant murine model

Department

Research

Document Type

Article

Publication Title

Vaccine

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 1-3weeks 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 7-8weeks of age with 1×10CFU of pneumococcal strain BG7322 (6A) or 1×10CFU of pneumococcal nontypeable strain 0702064MEF. Serum IgG titers were determined by ELISA. At 24 and 48h 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 48hpi (p=0.16). Vaccination with PcpA significantly reduced the bacterial burdens in MEF at both 24 (p=0.02) and 48hpi (p=0.004), and PlyD1 significantly reduced bacterial burden in MEF at 48hpi (p=0.02). Vaccination with trivalent PPrV (PhtD, PcpA and PlyD1) significantly reduced Spn burdens in MEF at both 24 (p=0.001) and 48hpi (p< 0.0001). Similar reductions of bacterial burdens were found when the vaccinated animals were challenged with a non-typeable Spn strain. Vaccinated mice had significantly milder inflammatory cytokine levels (IL-1β, IL-6, TNF-α, MIP-2 and KC) in middle ears at 24hpi (all p values< 0.05). CONCLUSION: Trivalent PPrV confers protection against pneumococcal AOM in an infant murine model.

First Page

337

Last Page

344

DOI

10.1016/j.vaccine.2016.11.046

Volume

35

Issue

2

Publication Date

1-5-2017

Medical Subject Headings

Animals; Animals, Newborn; Antibodies, Bacterial (blood); Bacterial Load; Bacterial Proteins (immunology); Colony Count, Microbial; Disease Models, Animal; Ear, Middle (microbiology); Enzyme-Linked Immunosorbent Assay; Exudates and Transudates (microbiology); Female; Immunoglobulin G (blood); Injections, Intramuscular; Male; Mice, Inbred C57BL; Otitis Media (prevention & control); Pneumococcal Infections (prevention & control); Pneumococcal Vaccines (administration & dosage, immunology); Streptococcus pneumoniae (immunology); Treatment Outcome; Vaccines, Subunit (administration & dosage, immunology); Vaccines, Synthetic (administration & dosage, immunology)

PubMed ID

27919628

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