Anderson Richard J, Hannan Carolyn M, Gilbert Sarah C, Laidlaw Stephen M, Sheu Eric G, Korten Simone, Sinden Robert, Butcher Geoffrey A, Skinner Michael A, Hill Adrian V S
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
J Immunol. 2004 Mar 1;172(5):3094-100. doi: 10.4049/jimmunol.172.5.3094.
Sterile immunity can be provided against the pre-erythrocytic stages of malaria by IFN-gamma-secreting CD8(+) T cells that recognize parasite-infected hepatocytes. In this study, we have investigated the use of attenuated fowlpox virus (FPV) strains as recombinant vaccine vectors for eliciting CD8(+) T cells against Plasmodium berghei. The gene encoding the P. berghei circumsporozoite (PbCS) protein was inserted into an FPV vaccine strain licensed for use in chickens, Webster's FPV, and the novel FPV vaccine strain FP9 by homologous recombination. The novel FP9 strain proved more potent as a vaccine for eliciting CD8(+) T cell responses against the PbCS Ag. Sequential immunization with rFP9 and recombinant modified vaccinia virus Anakara (MVA) encoding the PbCS protein, administered by clinically acceptable routes, elicited potent CD8(+) T cell responses against the PbCS protein. This immunization regimen elicited substantial protection against a stringent liver-stage challenge with P. berghei and was more immunogenic and protective than DNA/MVA prime/boost immunization. However, further improvement was not achieved by sequential (triple) immunization with a DNA vaccine, FP9, and MVA.
可通过识别被寄生虫感染的肝细胞的分泌γ干扰素的CD8(+) T细胞，针对疟疾的红细胞前期阶段提供无菌免疫。在本研究中，我们研究了使用减毒鸡痘病毒（FPV）株作为重组疫苗载体，以引发针对伯氏疟原虫的CD8(+) T细胞。通过同源重组，将编码伯氏疟原虫环子孢子（PbCS）蛋白的基因插入已获许可用于鸡的FPV疫苗株Webster's FPV和新型FPV疫苗株FP9中。新型FP9株作为引发针对PbCS抗原的CD8(+) T细胞应答的疫苗，被证明更有效。通过临床可接受的途径给予rFP9和编码PbCS蛋白的重组改良痘苗病毒安卡拉（MVA）进行序贯免疫，引发了针对PbCS蛋白的强效CD8(+) T细胞应答。这种免疫方案对伯氏疟原虫的严格肝期攻击产生了实质性保护，并且比DNA/MVA初免/加强免疫更具免疫原性和保护性。然而，通过DNA疫苗、FP9和MVA的序贯（三联）免疫并未实现进一步改善。
