Selvapandiyan Angamuthu, Duncan Robert, Debrabant Alain, Lee Nancy, Sreenivas G, Salotra Poonam, Nakhasi Hira L
Division of Emerging & Transfusion Transmitted Diseases, Office of Blood Research , Bethesda, MD 20892, USA.
Indian J Med Res. 2006 Mar;123(3):455-66.
Leishmaniasis causes significant morbidity and mortality worldwide and is an important public health problem. Even though it is endemic in developing countries in tropical regions of the world,in recent years economic globalization and increased travel has extended its reach to people in developed countries. Leishmania is usually spread by the bite of the female sandfly. In addition, naïve populations can be exposed to Leishmania infection through transfusion of blood and blood products from infected asymptomatic individuals. There are several clinical forms of leishmaniasis caused by different species of the parasite. In some cases, the only possible cure for this disease is drug treatment. However, prolonged use of such drugs has led to parasite drug resistance. At present there are no effective vaccines against Leishmania. Many vaccine strategies have been pursued, including the use of whole cell lysate, killed, avirulent or irradiated parasites. Additionally, DNA vaccines and purified or recombinant parasite antigens have also been tested. Most of these strategies have shown some degree of effectiveness in animal models but little or no protection in humans. There is now a general consensus among Leishmania vaccine researchers that parasite persistence may be important for effective protective response and could be achieved by live attenuated parasite immunization. In this article we reviewed the efforts in developing genetically defined live attenuated Leishmania parasites as vaccine candidates with the goal of achieving a low level of parasite persistence without being virulent in the host and inducing protective immunity.
利什曼病在全球范围内导致了严重的发病和死亡，是一个重要的公共卫生问题。尽管它在世界热带地区的发展中国家呈地方性流行，但近年来经济全球化和旅行增加使其传播范围扩大到了发达国家的人群。利什曼原虫通常通过雌性白蛉叮咬传播。此外，未感染过的人群可能通过输注来自无症状感染者的血液和血液制品而接触到利什曼原虫感染。由该寄生虫的不同种类引起的利什曼病有几种临床形式。在某些情况下，这种疾病唯一可能的治愈方法是药物治疗。然而，长期使用此类药物已导致寄生虫产生耐药性。目前尚无针对利什曼原虫的有效疫苗。人们已经探索了许多疫苗策略，包括使用全细胞裂解物、灭活的、无毒的或经辐射的寄生虫。此外，DNA疫苗以及纯化的或重组的寄生虫抗原也已进行了测试。这些策略大多在动物模型中显示出一定程度的有效性，但在人体中几乎没有或没有保护作用。利什曼病疫苗研究人员目前已达成普遍共识，即寄生虫的持续存在可能对有效的保护性反应很重要，并且可以通过减毒活寄生虫免疫来实现。在本文中，我们回顾了开发基因明确的减毒活利什曼原虫作为候选疫苗的努力，目标是在不具有宿主毒性的情况下实现低水平的寄生虫持续存在并诱导保护性免疫。
