Center for Infectious Disease Dynamics, Department of Biology, The Pennsylvania State University, University Park, Pennsylvania, United States of America.
PLoS Biol. 2012;10(7):e1001368. doi: 10.1371/journal.pbio.1001368. Epub 2012 Jul 31.
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 naïve 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.
疟疾疫苗的研发人员担心抗原逃逸会降低疫苗的效果。进化理论学家提出了这样一种可能性，即某些类型的疫苗也可能创造有利于更具毒性病原体进化的条件。这种进化将使未接种疫苗的人面临更严重疾病的风险增加。在这里，我们在实验室小鼠中测试了用单一高度纯化抗原接种疫苗对疟原虫 Plasmodium chabaudi 进化的影响。我们使用的抗原 AMA-1 是几种候选疟疾疫苗的成分，目前正处于人体临床试验的不同阶段。我们首先发现，一种更具毒性的克隆比其毒性较低的祖先更容易受到 AMA-1 诱导的免疫控制。然后，经过复制的寄生虫通过对照或 AMA-1 接种的小鼠连续传代，并在 10 轮和 21 轮选择后进行评估。我们没有在 ama-1 基因座发现进化的证据。相反，毒性发生了进化；与对照和祖先寄生虫相比，AMA-1 选择的寄生虫在未感染的小鼠中引起了更严重的贫血。我们的数据表明，重组血期疟疾疫苗可以驱动更具毒性的疟疾寄生虫的进化。
