Data from: The evolutionary consequences of blood-stage vaccination on the rodent malaria Plasmodium chabaudi

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.疟疾疫苗研发者担忧抗原逃逸（antigenic escape）会削弱疫苗效力。进化理论家曾提出，部分类型的疫苗可能会创造有利于毒力更强病原体演化的环境。此类演化将使未接种疫苗的人群面临更高的重症疾病风险。本研究针对实验室小鼠体内演化的查氏疟原虫（Plasmodium chabaudi），探究使用单一高纯度抗原进行疫苗接种的影响。我们所使用的抗原AMA-1，是目前多款处于人体临床试验不同阶段的候选疟疾疫苗的组成成分。我们首先发现，相较于毒力较弱的亲本克隆，毒力更强的克隆更难被AMA-1诱导的免疫反应所抑制。随后，我们将扩增得到的疟原虫通过对照组小鼠或接种AMA-1疫苗的小鼠进行连续传代，并在10轮和21轮筛选后对其展开评估。我们未在ama-1基因座中发现演化相关证据。与之相反，毒力出现演化：经AMA-1筛选的疟原虫在未致敏小鼠中诱导的贫血症状，相较于对照组及原始疟原虫均更为严重。本研究数据表明，重组红细胞期疟疾疫苗能够推动毒力更强的疟原虫的演化。