Experimental infection of rhesus macaques with Streptococcus pneumoniae: a possible model for vaccine assessment

J Med Primatol. 2006 Jun;35(3):113-22. doi: 10.1111/j.1600-0684.2006.00164.x.

Abstract

Background: We explored the possibility of using normal adult rhesus macaques for the preclinical assessment of safety, immunogenicity, and efficacy of newly developed vaccines against Streptococcus pneumoniae infection of the lung.

Methods: Our primary objective was to determine whether an intra-bronchial inoculum of at least 10(6)S. pneumoniae colony-forming units, or one as high as 10(8)-10(9) organisms, could detectably survive in rhesus macaques for a period longer than 1-2 weeks. If so, we hypothesized, it would be possible to observe signs of pneumonia commonly observed in humans, and discriminate between vaccinated/protected animals and controls. Infection was detectable in bronchoalveolar lavage fluids 3-5 weeks post-inoculation.

Results: The clinical course of disease mimicked aspects of that of human pneumococcal pneumonia. Signs of inflammation typical of the disease in humans, such as elevated concentrations of neutrophils and of pro-inflammatory cytokines in bronchoalveolar lavage fluids were also observed.

Conclusions: These findings underscore the utility of this model to assess the safety, immunogenicity, and efficacy of newly developed S. pneumoniae vaccines.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / immunology
  • Bronchoalveolar Lavage Fluid / microbiology
  • Colony Count, Microbial
  • Disease Models, Animal
  • Interleukin-1 / metabolism
  • Interleukin-6 / metabolism
  • Leukocyte Count
  • Longitudinal Studies
  • Macaca mulatta*
  • Male
  • Monkey Diseases / immunology*
  • Monkey Diseases / microbiology*
  • Monkey Diseases / prevention & control
  • Pneumococcal Vaccines / immunology
  • Pneumococcal Vaccines / pharmacology*
  • Pneumonia, Pneumococcal / immunology*
  • Pneumonia, Pneumococcal / microbiology
  • Pneumonia, Pneumococcal / prevention & control
  • Pneumonia, Pneumococcal / veterinary*
  • Streptococcus pneumoniae / immunology*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Interleukin-1
  • Interleukin-6
  • Pneumococcal Vaccines
  • Tumor Necrosis Factor-alpha