the evolutionary consequences of blood-stage vaccination on the rodent malaria plasmodium chabaudi的进化后果blood-stage啮齿动物疟原虫chabaudi疟疾疫苗接种.pdf

The Evolutionary Consequences of Blood-Stage Vaccination on the Rodent Malaria Plasmodium chabaudi 1 1 1 1 1 1 Victoria C. Barclay *, Derek Sim , Brian H. K. Chan , Lucas A. Nell , Maia A. Rabaa , Andrew S. Bell , Robin F. Anders2, Andrew F. Read1,3,4 1 Center for Infectious Disease Dynamics, Department of Biology, The Pennsylvania State University, University Park, Pennsylvania, United States of America, 2 Department of Biochemistry, La Trobe University, Melbourne, Australia, 3 Department of Entomology, The Pennsylvania State University, University Park, Pennsylvania, United States of America, 4 Fogarty International Center, National Institutes of Health, Bethesda, Maryland, United States of America Abstract 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