F Ndungu, Pwani University, Determining Cellular Correlates of Immunity to Malaria in an Experimental Human Challenge Model of Exposed Adults

点击翻译按钮获取中文摘要

Malaria, caused by Plasmodium falciparum parasites, remains a major public health problem in sub-Saharan Africa, affecting over 50% of the population. However, the current control efforts are hampered by a multiplicity of challenges including persistent threats of emerging drug and insecticide resistant parasites and mosquitoes, respectively, and logistical challenges owing to insufficient funding and poor health infrastructure. The main hope for the complete control that will bring down malaria transmission dramatically to the point where elimination is a reality is effective vaccination. However, despite decades of work, the development of an effective antimalarial vaccine has been problematic. Ironically, the substantial investment in developing anti-malaria vaccines has not been matched with similar levels of investment in understanding either the mechanisms of immunity to malaria, or the reasons the limited success with test vaccines. Although, children living with endemic malaria acquire immunity that initially protects them from severe malaria and death, and then recurring episodes of mild disease, the mechanisms that control the severity of symptoms, production of protective antibody, and parasite growth in the immune individual remain major knowledge gaps. Much of what we know today about immunity to malaria comes from animal and human field studies, which are hard to translate directly to the mechanisms that control infection inside the human body. In contrast, deliberate experimental infections of humans with malaria would give more relevant and direct information on the human immune response to infection. Our preliminary data demonstrated variable blood stage parasite growth rates following experimental infections of Kenya adults, and these rates were inversely correlated with the baseline levels of the individual's immunity, indicating that parasite growth rates can be accurate measures of the level of naturally acquired immunity. We are now conducting a prospective screen to determine correlates of antibody-based immunity following experimental human infections of Kenyan adults with different levels of baseline immunity. Because the cellular responses that confers immunity and participates in the mechanisms that produce protective antibodies are not known, I am proposing to take advantage of this unique opportunity to test which cellular responses correlate with the ability of an individual to control infection (inflammation and parasite growth) following experimental malaria infections in Kenyan adults. My study will identify patterns of immune responses that can be used as predictive markers of an individual's ability to control inflammation, produce protective levels of high quality antibodies, and to control parasite growth.