Immunogenicity and protective efficacy of a newly developed tri-component diphtheria, tetanus, and acellular pertussis vaccine in a murine model

J Microbiol Immunol Infect. 2018 Dec;51(6):732-739. doi: 10.1016/j.jmii.2017.04.003. Epub 2017 Jun 29.

Abstract

Background/purpose: Although assessing the immunogenicity and protective efficacy of acellular pertussis (aP) vaccines via murine model studies faces limitations, preliminary assessments have been achieved by evaluating respiratory challenge and humoral and cellular immunity.

Methods: We performed a long-term intranasal respiratory challenge with reference and clinically isolated strains of Bordetella pertussis. Simultaneously, we assessed humoral and cellular immunity for evaluating the immunogenicity of a newly developed tri-component diphtheria-tetanus-aP (DTaP) vaccine. Moreover, comparative assessment was made by performing the same evaluations with a commercially available tri-component DTaP vaccine as the positive control.

Results: Both groups showed significantly increased levels of antibodies against pertussis toxin, filamentous hemagglutinin and pertactin, and the levels of interferon-γ and interleukin-10 were significantly increased after two doses of vaccination. Furthermore, since cross cell-mediated immune reactivity between the two vaccines was detected, the possibility of interchangeability was indirectly suggested. Although the positive control group showed significantly higher titers in antibody responses for filamentous hemagglutinin and pertactin compared to the experimental group, anti-pertussis toxin antibody titers of the two groups were not significantly different and the protective efficacy against the clinical and reference strains was maintained in both groups for 18 weeks.

Conclusion: The results showed inferior immunogenicity of the new DTaP vaccine compared to a commercial vaccine despite comparable cellular immunity and protective efficacy. Some efforts are necessary for improving immunogenicity against filamentous hemagglutinin and pertactin before conducting human clinical trials.

Keywords: Diphtheria-tetanus-acellular pertussis vaccine; Efficacy; Immunogenicity; Mice.

Publication types

  • Comparative Study

MeSH terms

  • Adhesins, Bacterial / immunology
  • Animals
  • Antibodies, Bacterial / immunology
  • Bacterial Outer Membrane Proteins / immunology
  • Bordetella pertussis / immunology*
  • Cross Reactions
  • Diphtheria-Tetanus-Pertussis Vaccine / administration & dosage
  • Diphtheria-Tetanus-Pertussis Vaccine / immunology*
  • Disease Models, Animal*
  • Female
  • Immunization Schedule
  • Interferon-gamma / analysis
  • Interleukin-10 / analysis
  • Mice
  • Mice, Inbred BALB C
  • Pertussis Toxin / immunology
  • Virulence Factors, Bordetella / immunology
  • Whooping Cough / immunology*
  • Whooping Cough / prevention & control*

Substances

  • Adhesins, Bacterial
  • Antibodies, Bacterial
  • Bacterial Outer Membrane Proteins
  • Diphtheria-Tetanus-Pertussis Vaccine
  • IFNG protein, mouse
  • IL10 protein, mouse
  • Virulence Factors, Bordetella
  • filamentous hemagglutinin adhesin, Bordetella pertussis
  • Interleukin-10
  • pertactin
  • Interferon-gamma
  • Pertussis Toxin