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

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.