Waechter Alexander, Denner Joachim
Centre for HIV and Other Retroviruses, Robert Koch Institute, Nordufer 20, 13353, Berlin, Germany.
Immunol Res. 2014 Jan;58(1):9-19. doi: 10.1007/s12026-013-8430-y.
Previously, immunising different species with the transmembrane envelope protein p15E of the porcine endogenous retrovirus (PERV), neutralising antibodies were induced which recognised epitopes in the fusion peptide proximal region (FPPR) and in the membrane-proximal external region (MPER). Only the MPER-specific antibodies were shown to neutralise and these antibodies targeted epitopes in the MPER similarly localised as the epitopes recognised by antibodies broadly neutralising HIV-1 such as 2F5 and 4E10. To study whether neutralising antibodies could be induced immunising with subunits of p15E, recombinant proteins corresponding to the N-terminal, the C-terminal helical region (NHR, CHR) and a p15E with a mutation in the Cys-Cys loop were produced. Whereas none of these antigens induced MPER-specific neutralising antibodies, the animals immunised with the FPPR/NHR subunit and the mutated p15E produced neutralising antibodies binding to the NHR. Therefore, for the first time, antibodies specific for the NHR and neutralising PERV were described.
此前,用猪内源性逆转录病毒(PERV)的跨膜包膜蛋白p15E对不同物种进行免疫时,诱导产生了识别融合肽近端区域(FPPR)和膜近端外部区域(MPER)表位的中和抗体。只有MPER特异性抗体被证明具有中和作用,并且这些抗体靶向MPER中的表位,其定位与被广泛中和HIV-1的抗体(如2F5和4E10)所识别的表位相似。为了研究用p15E亚基进行免疫是否能诱导产生中和抗体,制备了对应于N端、C端螺旋区域(NHR、CHR)的重组蛋白以及在半胱氨酸-半胱氨酸环处有突变的p15E。尽管这些抗原均未诱导产生MPER特异性中和抗体,但用FPPR/NHR亚基和突变型p15E免疫的动物产生了与NHR结合的中和抗体。因此,首次描述了对NHR具有特异性且能中和PERV的抗体。