Robinson Cory M, Kobe Brianna N, Schmitt Deanna M, Phair Brian, Gilson Tricia, Jung Joo-Yong, Roberts Lawton, Liao Jialin, Camerlengo Chelsea, Chang Brandon, Davis Mackenzie, Figurski Leah, Sindeldecker Devin, Horzempa Joseph
a Biomedical Sciences Department ; West Virginia School of Osteopathic Medicine ; Lewisburg , WV USA.
Bioengineered. 2015;6(2):82-8. doi: 10.1080/21655979.2015.1011033.
Francisella tularensis LVS (Live Vaccine Strain) is an attenuated bacterium that has been used as a live vaccine. Patients immunized with this organism show a very long-term memory response (over 30 years post vaccination) evidenced by the presence of indicators of robust cell-mediated immunity. Because F. tularensis LVS is such a potent vaccine, we hypothesized that this organism would be an effective vaccine platform. First, we sought to determine if we could genetically modify this strain to produce protective antigens of a heterologous pathogen. Currently, there is not a licensed vaccine against the important opportunistic bacterial pathogen, Pseudomonas aeruginosa. Because many P. aeruginosa strains are also drug resistant, the need for effective vaccines is magnified. Here, F. tularensis LVS was genetically modified to express surface proteins PilAPa, OprFPa, and FliCPa of P. aeruginosa. Immunization of mice with LVS expressing the recombinant FliCPa led to a significant production of antibodies specific for P. aeruginosa. However, mice that had been immunized with LVS expressing PilAPa or OprFPa did not produce high levels of antibodies specific for P. aerugionsa. Therefore, the recombinant LVS strain engineered to produce FliCPa may be able to provide immune protection against a P. aeruginosa challenge. However for future use of this vaccine platform, selection of the appropriate recombinant antigen is critical as not all recombinant antigens expressed in this strain were immunogenic.
土拉弗朗西斯菌LVS（活疫苗株）是一种减毒细菌，已被用作活疫苗。用这种生物体免疫的患者表现出非常长期的记忆反应（接种疫苗后超过30年），这通过强大的细胞介导免疫指标的存在得到证明。由于土拉弗朗西斯菌LVS是一种如此有效的疫苗，我们假设这种生物体将是一个有效的疫苗平台。首先，我们试图确定是否可以对该菌株进行基因改造，以产生异源病原体的保护性抗原。目前，尚无针对重要机会性细菌病原体铜绿假单胞菌的许可疫苗。由于许多铜绿假单胞菌菌株也具有耐药性，对有效疫苗的需求更加迫切。在这里，土拉弗朗西斯菌LVS经过基因改造，以表达铜绿假单胞菌的表面蛋白PilAPa、OprFPa和FliCPa。用表达重组FliCPa的LVS免疫小鼠导致产生大量针对铜绿假单胞菌的特异性抗体。然而，用表达PilAPa或OprFPa的LVS免疫的小鼠没有产生高水平的针对铜绿假单胞菌的特异性抗体。因此，经过基因工程改造以产生FliCPa的重组LVS菌株可能能够提供针对铜绿假单胞菌攻击的免疫保护。然而，对于该疫苗平台的未来应用，选择合适的重组抗原至关重要，因为并非该菌株中表达的所有重组抗原都具有免疫原性。
