人工多表位嵌合抗原用于恶性疟疾血清学监测的可行性研究-病原上生物学专业毕业论文.docx

北京协和医学院博士研究生学位论文Multi-epitope 北京协和医学院博士研究生学位论文 Multi-epitope chimeric antigen used as a serological marker for estimating Plasmodium falciparum transmission intensity Meixue Yao (Institute ofBasic Medical Sciences，Chinese Academy ofMedical Sciences，100005，Beijing) Abstract Following the decline of malaria transmission in many countries and regions， entomological estimates becomes less sensitive，and serological parameters becomes particular useful for malaria surveillance especially in low intensity areas．However, whether an appropriate serological marker can be selected is the critical core of this method．Various malaria antigens has been used as the serological markers，such AMA-1， MSP-2 and MSP-1 1 9．however,each of them has its own 1imitations． Our lab has been successfully constructed two multi—epitope chimeric proteins， Malaria Random Constructed Antigen一1(M．RCAg-1)and M．RCAg-3，which contains 1 1 and 1 5 relatively conservative epitopes from 8 antigens of Plasmodium falciparum， respectively．We selected M．RCAg-1 as the serological marker through comparing their sensitivety to the naturally acquired anti—malaria antibodies．Here we demonstrated that M．RCAg-1 is high sensitive to the naturally acquired anti-malaria antibodies，and has the advantage of less polymorphism．The half-live of the anti—M．RCAg-1 antibodies fell into the range ofweeks to months． The anti—M．RCAg-1 antibody level were significantly higher in populations from the China-Myanmar border than that from Beijing，and no significant different was found between individuals from Hainan or Beijing．The P．falciparum malaria transmission intensity(SCR)estimated with M．RCAg-1 in this study is linearly correlated with the EIR， which provides great evidence that the availability of M．RCAg一1 can be used to estimate the malaria transmission intensity． Our preliminary data support that the chimeric antigen，M．RCAg一1 has the potential to be used as fl sero—surveillance tool in estimating the rencent P．falciparum malar