Cardona P J, Asensio J Gonzalo, Arbués A, Otal I, Lafoz C, Gil O, Caceres N, Ausina V, Gicquel B, Martin C
Institut "Germans Trias i Pujol", Badalona, Spain.
Vaccine. 2009 Apr 21;27(18):2499-505. doi: 10.1016/j.vaccine.2009.02.060. Epub 2009 Feb 24.
Safety is one of the main concerns for attenuated live vaccine candidates. Here we extend the stability and attenuation studies of the promising tuberculosis vaccine candidate based on Mycobacterium tuberculosis phoP mutant strain, SO2. Stability of the phoP mutation was tested after sub-culturing SO2 strain for 6 months in laboratory media and also after 3 months of infection in SCID mice. Results showed no reversion of the phoP mutation either in vitro or in vivo. In addition, SO2 was fully sensitive to four major first-line antituberculous drugs against tuberculosis. Safety and toxicity studies were performed in guinea pigs. Animals were infected with a quantity of SO2 equivalent to 50 vaccination doses (2.5x10(6) CFUs) and weight was monitored for 6 months. All animals survived and no histological lesions were found, showing full attenuation of SO2. Studies in a post-exposure model of guinea pigs and mice, previously infected with M. tuberculosis, were performed and no toxicity effects were found after inoculation of SO2. All these results together confirm that SO2 has a secure safety profile that encourages its use in clinical trials.
安全性是减毒活疫苗候选株的主要关注点之一。在此，我们扩展了对基于结核分枝杆菌phoP突变株SO2的有前景的结核病疫苗候选株的稳定性和减毒研究。在实验室培养基中对SO2菌株进行6个月传代培养后，以及在SCID小鼠中感染3个月后，测试了phoP突变的稳定性。结果表明，phoP突变在体外或体内均未发生回复突变。此外，SO2对四种主要的一线抗结核药物完全敏感。在豚鼠中进行了安全性和毒性研究。用相当于50个疫苗剂量（2.5×10⁶CFU）的SO2感染动物，并监测其体重6个月。所有动物均存活，未发现组织学病变，表明SO2完全减毒。在先前感染结核分枝杆菌的豚鼠和小鼠的暴露后模型中进行了研究，接种SO2后未发现毒性作用。所有这些结果共同证实，SO2具有可靠的安全性，这鼓励其用于临床试验。
