Experimental infection of rhesus macaques with Streptococcus pneumoniae: a possible model for vaccine assessment.
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.
Philipp
Mario T
MT
Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, LA 70433, USA. philipp@tpc.tulane.edu
Purcell
Jeanette E
JE
Martin
Dale S
DS
Buck
Wayne R
WR
Plauché
Gail B
GB
Ribka
Erin P
EP
DeNoel
Philippe
P
Hermand
Philippe
P
Leiva
Lily E
LE
Bagby
Gregory J
GJ
Nelson
Steve
S
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology / Q000382:microbiology; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007958:Leukocyte Count; D008137:Longitudinal Studies; D008253:Macaca mulatta; D008297:Male; D008992:Monkey Diseases / Q000276:immunology* / Q000382:microbiology* / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000276:immunology / Q000494:pharmacology*; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control / Q000662:veterinary*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007375:Interleukin-1; D015850:Interleukin-6; D022242:Pneumococcal Vaccines; D014409:Tumor Necrosis Factor-alpha