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Vaccine Detail

Nontypeable H. influenzae Outer Membrane Protein P1 vaccine
Vaccine Information
  • Vaccine Name: Nontypeable H. influenzae Outer Membrane Protein P1 vaccine
  • Target Pathogen: Haemophilus influenzae
  • Target Disease: Meningitis
  • Vaccine Ontology ID: VO_0004110
  • Type: Subunit vaccine
  • Antigen: Outer Membrane Protein P1
  • ompP1 gene engineering:
    • Type: Recombinant protein preparation
    • Description:
    • Detailed Gene Information: Click Here.
  • Adjuvant:
  • Preparation: OmpP1 was cloned from the clinical NTHI strain BCH-3 and expressed P1 in the cytoplasm of E. coli (rP1BCH-3 ).
  • Description: OMP P1 (47 kDa) accounts for ~10% of H. influenzae OMP content. Passive immunization with P1 induces protection against bacteremia in the infant rat model. OMP P1 has eight potentially surface-exposed loops, four of which are immunogenic. The availability of several ompP1 sequences was particularly relevant, as it offered the information needed for a broader survey of the sequence conservation of the ompP1 gene across a phylogenically classified collection of >500 typeable H. influenzae and NTHI isolates representing the natural population structure of the species (Bolduc et al., 2000).
Host Response

chinchillas Response

  • Vaccination Protocol: rP1BCH-3 was emulsified in RIBI adjuvant R-730 emulsion (RIBI Immunochem Research) to a final rP1BCH-3 concentration of 125 µg/ml. Twenty-eight chinchillas were immunized with two 0.1-ml intramuscular (i.m.) injections in the hindquarters on days 0, 35, 57, 79, 99, 120, and 141. Eight control chinchillas received two 0.1-ml i.m. injections of RIBI adjuvant only on the same days. All chinchillas were bled by cardiac puncture using a 23-gauge 3-ml syringe on days 0 (before receiving the first immunization) and 148 (prior to challenge) (Bolduc et al., 2000).
  • Challenge Protocol: Seven days after the final immunization, four nonimmunized chinchillas were added to the experimental group as controls. All animals were examined by otoscopy and tympanometry to document healthy, normal middle ears. Loopfuls of wt strain BCH-3 and the isogenic BCH-3 ompP1 mutant were inoculated separately into 1 ml of supplemented brain heart infusion medium and incubated without agitation for 16 to 18 h at 37°C. Overnight cultures were diluted by 2 × 10-3 in Gey's balanced salt solution (Sigma). The chinchillas were divided into two groups. One group was challenged with wt BCH-3, and the other was challenged with the BCH-3 ompP1 mutant by injecting 0.1 ml of the diluted cultures containing 50 to 60 CFU directly into the right middle-ear cavity through the superior bulla with a tuberculin syringe. Chinchillas were reexamined by otoscopy and tympanometry on days 2, 4, 6, 8, 10, 14, and 18. On these days, the middle-ear cavities were also examined through a small (4 mm in diameter) incision in the superior bulla, leaving the tympanic membrane intact. The right middle-ear cavities were cultured by swabbing the cavity with a calcium alginate swab (Calgiswab type 1; Hardwood Products Company LP) and streaking onto chocolate agar plates (Bolduc et al., 2000).
  • Efficacy: all animals developed antibodies specific for rP1. Immunized animals were protected against disease when challenged with BCH-3, but not with an ompP1 mutant of BCH-3 or a strain (BCH-2) possessing a heterologous P1 (91% identity).
References
Bolduc et al., 2000: Bolduc GR, Bouchet V, Jiang RZ, Geisselsoder J, Truong-Bolduc QC, Rice PA, Pelton SI, Goldstein R. Variability of outer membrane protein P1 and its evaluation as a vaccine candidate against experimental otitis media due to nontypeable Haemophilus influenzae: an unambiguous, multifaceted approach. Infection and immunity. 2000 Aug; 68(8); 4505-17. [PubMed: 10899849].