Philipp Mario T, Purcell Jeanette E, Martin Dale S, Buck Wayne R, Plauché Gail B, Ribka Erin P, DeNoel Philippe, Hermand Philippe, Leiva Lily E, Bagby Gregory J, Nelson Steve
Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, LA 70433, USA.
J Med Primatol. 2006 Jun;35(3):113-22. doi: 10.1111/j.1600-0684.2006.00164.x.
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.
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.
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.
These findings underscore the utility of this model to assess the safety, immunogenicity, and efficacy of newly developed S. pneumoniae vaccines.
我们探讨了使用正常成年恒河猴对新开发的抗肺炎链球菌肺部感染疫苗进行安全性、免疫原性和有效性临床前评估的可能性。
我们的主要目标是确定至少10⁶肺炎链球菌集落形成单位的支气管内接种物，或高达10⁸ - 10⁹个菌体的接种物，是否能在恒河猴体内存活超过1 - 2周并被检测到。如果可以，我们推测，就有可能观察到人类常见的肺炎症状，并区分接种/受保护动物和对照组。接种后3 - 5周，在支气管肺泡灌洗液中可检测到感染。
疾病的临床过程模拟了人类肺炎球菌肺炎的某些方面。在支气管肺泡灌洗液中也观察到了人类该疾病典型的炎症迹象，如中性粒细胞和促炎细胞因子浓度升高。
这些发现强调了该模型在评估新开发的肺炎链球菌疫苗的安全性、免疫原性和有效性方面的实用性。
