Antibodies against a secreted protein from hookworm larvae reduce the intensity of hookworm infection in humans and vaccinated laboratory animals
Antibodies against a secreted protein from hookworm larvae reduce the intensity of hookworm infection in humans and vaccinated laboratory animals
复制标题
DOI：
10.1096/fj.05-3936fje
复制
发表时间：
2005-07-01
期刊：
影响因子：
4.8
通讯作者：
Hotez, PJ
中科院分区：
文献类型：
--
作者：
Bethony, J;Loukas, A;Hotez, PJ
疫苗的开发将为控制人类钩虫感染提供重要的新工具。成功的基础上接种活的辐照，第三阶段的钩虫幼虫（L3）的实验室动物，我们研究了个体的抗体反应，从钩虫流行地区的巴西和中国对最丰富的L3分泌抗原，钩虫分泌蛋白，ASP-1和ASP-2。Logistic回归被用来调查抗体同种型反应的影响，以ASP的风险，个人窝藏重钩虫感染。抗ASP-2 IgE水平升高与钩虫重度感染风险之间存在显著的保护性相关性。为了确认ASP-2是保护性抗原，用GlaxoSmithKline佐剂AS 03配制的重组ASP-2免疫实验室犬。从免疫狗获得的血清表现出高几何平均抗体滴度，免疫沉淀来自L3提取物的天然ASP-2，并将ASP-2表达位点定位于腺食道和退出角质层的身体通道。相对于来自注射AS 03的对照的血清，血清还表现出体外抑制L3通过组织迁移的能力增加。L3攻毒后，ASP-2免疫犬的粪便虫卵计数和肠道钩虫负荷显著降低。这些发现为开发有效的抗人类钩虫感染的重组疫苗提供了强有力的支持。
The development of a vaccine would provide an important new tool for the control of human hookworm infection. On the basis of successful vaccination of laboratory animals with living irradiated, third-stage hookworm larvae (L3), we examined the antibody responses of individuals from hookworm endemic areas of Brazil and China against the most abundant L3 secreted antigens, the ancylostoma secreted proteins, ASP-1 and ASP-2. Logistic regression was used to investigate the effects of antibody isotype responses to ASPs on the risk of an individual harboring heavy hookworm infection. A significant protective association was observed between increasing anti-ASP-2 IgE levels and the risk of heavy hookworm infection. To confirm that ASP-2 is a protective antigen, laboratory dogs were immunized with recombinant ASP-2 formulated with the GlaxoSmithKline Adjuvant, AS03. Sera obtained from the immunized dogs exhibited high geometric mean antibody titers, immunoprecipitated native ASP-2 from L3 extracts and localized the site of ASP-2 expression to the glandular esophagus and body channels exiting to the cuticle. The sera also exhibited an increased ability to inhibit migration of L3 through tissue in vitro relative to sera from AS03-injected controls. Upon L3 challenge, the ASP-2 vaccinated dogs exhibited significant reductions in fecal egg counts and intestinal hookworm burden. These findings provide strong support for the development of an effective recombinant vaccine against hookworm infection in humans.