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[抗登革热免疫制剂的研发]

[Development of immunizing agents against dengue].

作者信息

López Antuñano F J, Mota J

机构信息

Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México.

出版信息

Rev Panam Salud Publica. 2000 May;7(5):285-92. doi: 10.1590/s1020-49892000000500001.

DOI:10.1590/s1020-49892000000500001
PMID:10893968
Abstract

The four serotypes of dengue flaviviruses are transmitted mainly by the Aedes aegypti mosquito, and some epidemics have been attributed to Ae. albopictus, Ae. polynesiensis, and various species of the Ae. scutellaris complex. The risk factors involved in dengue mortality and morbidity are related to the human host (genetic characteristics of infected persons; lifestyles, immune status, and health conditions of people; basic sanitation of dwellings; and water supply) and to the virus (genetic variability between and among serotypes, different pathogenicities, and geographic distribution). Notwithstanding the lack of knowledge of the immunopathobiology of dengue fever, important advances have been made in terms of a protective immune response, using attenuated dengue viruses or antigens produced by means of recombinant technologies. Efforts have been made since the 1940s to develop dengue vaccines. Immunity acquired from natural infection is specific for each serotype, and as many as three different serotype infections have been reported in one individual. For this reason, a tetravalent vaccine may likely be needed. Candidate vaccines against the four serotypes have been tested in volunteers and have proven to be immunogenic and safe. Although attenuated live virus vaccines are promising, more study is needed regarding their effectiveness and safety. Currently, several studies are ongoing to develop dengue vaccines using antigens from structural proteins (particularly E glycoprotein) and nonstructural proteins, with recombinant DNA technology and other biomolecular technologies. With the same goal, various expression vectors are being used, including Escherichia coli, baculovirus, vaccinia virus, and yellow fever virus. Unfortunately, no satisfactory results have been obtained in humans. The need for effective dengue vaccines is great, given the serious worldwide problem of the transmission of the four serotypes. Effective immunization against dengue would contribute to its prevention, with a positive cost-benefit relationship. Endemic dengue affects young children, and they should be immunized through the Expanded Program on Immunization.

摘要

登革热黄病毒的四种血清型主要通过埃及伊蚊传播,一些疫情被归因于白纹伊蚊、波利尼西亚伊蚊以及盾纹伊蚊复合体的各种物种。登革热死亡率和发病率相关的风险因素与人类宿主(感染者的遗传特征;人们的生活方式、免疫状态和健康状况;住所的基本卫生条件;以及供水情况)和病毒(血清型之间和之内的遗传变异性、不同的致病性以及地理分布)有关。尽管对登革热的免疫病理生物学缺乏了解,但在使用减毒登革热病毒或通过重组技术生产的抗原方面,在保护性免疫反应方面已经取得了重要进展。自20世纪40年代以来一直在努力研发登革热疫苗。自然感染获得的免疫力对每种血清型都是特异性的,并且据报道一个人身上可能会有多达三种不同血清型的感染。因此,可能需要一种四价疫苗。针对四种血清型的候选疫苗已在志愿者身上进行了测试,并已证明具有免疫原性且安全。尽管减毒活病毒疫苗很有前景,但仍需要对其有效性和安全性进行更多研究。目前,正在进行多项研究,利用结构蛋白(特别是E糖蛋白)和非结构蛋白的抗原,通过重组DNA技术和其他生物分子技术来研发登革热疫苗。出于同样的目的,正在使用各种表达载体,包括大肠杆菌、杆状病毒、痘苗病毒和黄热病毒。不幸的是,在人体中尚未获得令人满意的结果。鉴于四种血清型传播的严重全球问题,对有效登革热疫苗的需求很大。对登革热进行有效的免疫接种将有助于预防登革热,具有积极的成本效益关系。地方性登革热影响幼儿,应通过扩大免疫规划对他们进行免疫接种。

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