Malaria Vaccine: AMA1-C2

疟疾疫苗发展处(MVDB)是NIAID的一项倡议，与DMID密切合作，以满足全球对疟疾疫苗的需求。MVDB于2001年被委托研究、开发和生产疟疾疫苗原型，并对有希望的候选疫苗进行早期临床试验。我们的总体目标是开发疟疾疫苗，以减少非洲儿童的严重疾病和死亡，并在世界低传播率地区消除疟疾。 一种无性血液期疫苗将引发免疫反应，能够摧毁血液中的疟疾寄生虫，或抑制寄生虫感染红细胞。在任何一种情况下，净效果都是减轻或预防寄生虫的负担，从而减少疾病的发生率、严重性或并发症。这种疫苗将针对血液阶段的寄生虫蛋白，因为在持续感染期间，寄生虫会大量表达这些抗原。它将起到为婴儿随后感染的免疫系统做准备的作用，或者它将增强幼儿已经存在但却很弱的自然免疫力。此外，由多种抗原组成的疫苗将增加对疫苗中至少一个成分有反应的个体数量。多态蛋白的多个等位基因的包含也将使寄生虫选择的免疫压力降至最低，从而降低寄生虫突破的可能性。 已经完成了几项动物研究，以评估AMA1-C2疫苗。抗血清对3个等位基因均有效。目前的努力集中在临床级别疫苗的生产和表征，以及为在美国进行第一阶段试验准备IND。

The Malaria Vaccine Development Branch (MVDB) is an NIAID initiative working in close collaboration with DMID to respond to the global need for vaccines against malaria. The MVDB was commissioned in 2001 to research, develop, and produce prototype malaria vaccines and conduct early-phase clinical trials of promising vaccine candidates. Our overarching goal is to develop malaria vaccines that will reduce severe disease and death among African children and eliminate malaria from low-transmission areas of the world. An asexual blood-stage vaccine will elicit immune responses capable of either destroying malaria parasites in the blood stream or inhibiting parasites from infecting red blood cells. In either case, the net effect is to reduce or prevent burden of parasites and hence decrease the incidence, severity, or the complications of disease. Such a vaccine would target blood-stage parasite proteins since these antigens are abundantly expressed by parasites during persistent infections. It would act to prime the immune system for subsequent infection in infants or it would boost already present, yet weak, natural immunity in young children. Furthermore, a vaccine composed of multiple antigens will increase the number of individuals responding to at least one component of the vaccine. The inclusion of multiple alleles of polymorphic proteins would also minimize immune pressure on parasite selection, thus decreasing the likelihood of parasite breakthrough. Several animal studies have been completed to evaluate the AMA1-C2 vaccine. The antisera were effective in GIA against all 3 alleles. Current efforts are focused on production and characterization of clinical grade vaccine, and preparation of an IND for conducting a Phase 1 trial in US.