Geographical structure of diversity and differences between symptomatic and asymptomatic infections for Plasmodium falciparum vaccine candidate AMA1

被引:108
作者
Cortes, A
Mellombo, M
Mueller, I
Benet, A
Reeder, JC
Anders, RF
机构
[1] Papua New Guinea Inst Med Res, Madang, Papua N Guinea
[2] Papua New Guinea Inst Med Res, Goroka, Papua N Guinea
[3] La Trobe Univ, Cooperat Res Ctr Vaccine Technol, Dept Biochem, Melbourne, Vic 3086, Australia
关键词
D O I
10.1128/IAI.71.3.1416-1426.2003
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Plasmodium falciparum apical membrane antigen 1 (AMA1) is a prime malaria vaccine candidate. Antigenic diversity within parasite populations is one of the main factors potentially limiting the efficacy of any asexual-stage vaccine, including one based on AMA1. The DNA coding for the most variable region of this antigen, domain 1, was sequenced in 168 samples from the Wosera region of Papua New Guinea, including samples from symptomatic and asymptomatic infections. Neutrality tests applied to these sequences provided strong evidence of selective pressure operating on the sequence of ama1 domain 1, consistent with AMA1 being a target of protective immunity. Similarly, a peculiar pattern of geographical diversity and the particular substitutions found were suggestive of strong constraints acting on the evolution of AMA1 at the population level, probably as a result of immune pressure. In addition, a strong imbalance between symptomatic and asymptomatic infections was detected in the frequency of particular residues at certain polymorphic positions, pointing to AMA1 as being one of the determinants of the morbidity associated with a particular strain. The information yielded by this study has implications for the design and assessment of AMA1-based vaccines and provides additional data supporting the importance of AMA1 as a malaria vaccine candidate.
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收藏
页码:1416 / 1426
页数:11
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