Disruption of antigenic variation is crucial for effective parasite vaccine

Rivero FD, et al. 2010. Nat. med. 16(5), 551-557.

Speaker: Yu-Cheng Lin (林祐丞)                                  Time: 13:00~14:00, Sept. 29, 2010

Commentator: Ching-Chuan Liu (劉清泉 老師) Place: Room 601

Abstract:

Giardia lamblia, a human intestinal pathogen causing giardiasis, is one of the most common causes of intestinal disease worldwide. Like many other protozoan pathogens, Giardia undergoes antigenic variation to evade immune response of the hosts for producing chronic and recurrent infections. The major antigens inducing strongly humoral immune response of the hosts are variant-specific surface proteins (VSPs) ¹. From a repertoire of ~190 VSP-coding genes in the genome, most of VSPs are transcribed simultaneously, but only one VSP is expressed on surface of Giardia at a particular time, and spontaneously switches to different forms of VSPs for antigenic variation². The authors had found that such the mechanism controlling VSP switching involves the component of RNA interference machinery³, and they constructed the transgenic clones to generate trophozoites simultaneously expressing many VSPs by disrupting this RNA interference pathway. By using these transgenic parasites and gerbils model of giardiasis, they showed that either primary infection with trophozoites simultaneously expressing many VSPs or immunization with purified VSPs from the transgenic parasites protects gerbils from subsequent Giardia infections. These results demonstrated that the VSPs purified from the transgenic parasites have potential to develop vaccines to decrease the severe infection of giardiasis. The novelty of this study is that the authors are the first establishing experimental evidence that antigenic variation is essential for parasite survival in host, and that antigenic variation could probably be artificially disrupted to develop useful vaccines against pathogens that have similar mechanism.

References:

1.      Nash, TE. 1997. Antigenic variation in Giardia lamblia and the host’s immune response. Phil. Trans. R. Soc. Lond. 352, 1369-1375.

2.      Deitsch, KW, Lukehart, SA & Stringer, JR. 2009. Common strategies for antigenic variation by bacterial, fungal and protozoan pathogens. Nat. Rev. Microbiol. 7, 493-503.

3.      Prucca, CG. et al. 2008. Antigenic variation in Giardia lamblia is regulated by RNA interference. Nature. 456, 750-754.