The Evolutionary Consequences of Blood-Stage Vaccination on the Rodent Malaria Plasmodium chabaudi

被引:44
|
作者
Barclay, Victoria C. [1 ]
Sim, Derek [1 ]
Chan, Brian H. K. [1 ]
Nell, Lucas A. [1 ]
Rabaa, Maia A. [1 ]
Bell, Andrew S. [1 ]
Anders, Robin F. [2 ]
Read, Andrew F. [1 ,3 ,4 ]
机构
[1] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA
[2] La Trobe Univ, Dept Biochem, Melbourne, Vic, Australia
[3] Penn State Univ, Dept Entomol, University Pk, PA 16802 USA
[4] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA
来源
PLOS BIOLOGY | 2012年 / 10卷 / 07期
基金
英国惠康基金;
关键词
APICAL MEMBRANE ANTIGEN-1; PAPUA-NEW-GUINEA; BORDETELLA-PERTUSSIS STRAINS; MAREKS-DISEASE VACCINES; WITHIN-HOST COMPETITION; IMMUNOGENICITY TRIAL; POPULATION-STRUCTURE; VIRULENCE EVOLUTION; PROTECTIVE IMMUNITY; TEMPORAL TRENDS;
D O I
10.1371/journal.pbio.1001368
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Malaria vaccine developers are concerned that antigenic escape will erode vaccine efficacy. Evolutionary theorists have raised the possibility that some types of vaccine could also create conditions favoring the evolution of more virulent pathogens. Such evolution would put unvaccinated people at greater risk of severe disease. Here we test the impact of vaccination with a single highly purified antigen on the malaria parasite Plasmodium chabaudi evolving in laboratory mice. The antigen we used, AMA-1, is a component of several candidate malaria vaccines currently in various stages of trials in humans. We first found that a more virulent clone was less readily controlled by AMA-1-induced immunity than its less virulent progenitor. Replicated parasites were then serially passaged through control or AMA-1 vaccinated mice and evaluated after 10 and 21 rounds of selection. We found no evidence of evolution at the ama-1 locus. Instead, virulence evolved; AMA-1-selected parasites induced greater anemia in naive mice than both control and ancestral parasites. Our data suggest that recombinant blood stage malaria vaccines can drive the evolution of more virulent malaria parasites.
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页数:11
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