Lal A A, de la Cruz V F, Good M F, Weiss W R, Lunde M, Maloy W L, Welsh J A, McCutchan T F
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1987 Dec;84(23):8647-51. doi: 10.1073/pnas.84.23.8647.
To test the putative in vivo protective effects of antibodies to circumsporozoite (CS) protein repeats against malarial infection, different strains of mice were immunized against various repetitive regions of the Plasmodium yoelii CS protein in the form of synthetic peptides conjugated to keyhole limpet hemocyanin. Complete Freund's adjuvant or saponin was used as adjuvant. When vaccinated mice were challenged with 500 sporozoites almost all animals became infected. There were no significant protective effects in vaccinated versus unvaccinated mice. Furthermore, there was no correlation between the antibody titer to the CS repeats and infection. The parasites from infected animals were shown to encode a CS protein containing the same repeats as those used for immunization, indicating that the infections were not due to selection for variant parasites. These experiments demonstrate that antibodies to the CS repeats, as derived in vivo with peptides, despite being surface reactive, do not provide protection against sporozoite challenge in vivo. This conclusion is in contrast to previous conclusions based on studies showing protection by way of in vitro sporozoite neutralization procedures and passive transfer of monoclonal antibody.
为了测试针对环子孢子（CS）蛋白重复序列的抗体对疟疾感染的假定体内保护作用，以与钥孔血蓝蛋白偶联的合成肽形式，用约氏疟原虫CS蛋白的各种重复区域对不同品系的小鼠进行免疫。使用完全弗氏佐剂或皂苷作为佐剂。当用500个子孢子攻击接种疫苗的小鼠时，几乎所有动物都被感染。接种疫苗的小鼠与未接种疫苗的小鼠相比没有显著的保护作用。此外，针对CS重复序列的抗体效价与感染之间没有相关性。来自感染动物的寄生虫显示编码一种含有与用于免疫的重复序列相同的CS蛋白，表明感染不是由于选择变异寄生虫所致。这些实验表明，体内由肽产生的针对CS重复序列的抗体，尽管具有表面反应性，但在体内不能提供针对子孢子攻击的保护作用。这一结论与先前基于体外子孢子中和程序和单克隆抗体被动转移显示有保护作用的研究得出的结论相反。
