Department of Medical Parasitology, New York University School of Medicine, 341 East 25th Street, New York, NY 10010, USA.
Malar J. 2010 Dec 15;9:362. doi: 10.1186/1475-2875-9-362.
Intravenous injection of mice with attenuated Plasmodium berghei sporozoites induces sterile immunity to challenge with viable sporozoites. Non-intravenous routes have been reported to yield poor immunity. Because intravenous immunization has been considered to be unacceptable for large scale vaccination of humans, assessment was made of the results of intradermal immunization of mice with Plasmodium yoelii, a rodent malaria parasite whose infectivity resembles that of human malaria.
Mice were immunized with two injections of isolated, radiation-attenuated P. yoelii sporozoites, either by intravenous (IV) or intradermal (ID) inoculation. In an attempt to enhance protective immunogenicity of ID-injections, one group of experimental mice received topical application of an adjuvant, Imiquimod, while another group had their injections accompanied by local "tape-stripping" of the skin, a procedure known to disrupt the stratum corneum and activate local immunocytes. Challenge of immunized and non-immunized control mice was by bite of sporozoite-infected mosquitoes. Degree of protection among the various groups of mice was determined by microscopic examination of stained blood smears. Statistical significance of protection was determined by a one-way ANOVA followed by Tukey's post hoc test.
Two intravenous immunizations produced 94% protection to mosquito bite challenge; intradermal immunization produced 78% protection, while intradermal immunization accompanied by "tape-stripping" produced 94% protection. There were no statistically significant differences in degree of protective immunity between immunizations done by intravenous versus intradermal injection.
The use of a sub-microlitre syringe for intradermal injections yielded excellent protective immunity. ID-immunization with large numbers of radiation-attenuated P. yoelii sporozoites led to levels of protective immunity comparable to those achieved by IV-immunization. It remains to be determined whether an adjuvant treatment can be found to substantially reduce the numbers of attenuated sporozoites required to achieve a strong protective immunity with as few doses as possible for possible extension to immunization of humans.
经静脉注射减毒疟原虫孢子可诱导对活孢子的无菌免疫。已有报道称，非静脉途径产生的免疫效果不佳。由于静脉免疫被认为不适用于大规模人类疫苗接种，因此评估了经皮（皮内）免疫感染性疟原虫（鼠疟原虫）的结果。感染性疟原虫类似于人类疟疾。
通过静脉（IV）或皮内（ID）接种，用分离的、辐射减毒的疟原虫孢子对小鼠进行两次免疫。为了增强 ID 注射的保护免疫原性，一组实验小鼠接受了咪喹莫特（一种免疫佐剂）的局部应用，另一组则在注射的同时进行皮肤“胶带剥离”，这一过程已知会破坏角质层并激活局部免疫细胞。用感染孢子的疟蚊叮咬免疫和非免疫对照小鼠进行攻击。通过对染色血涂片进行显微镜检查来确定不同组小鼠的保护程度。用单向方差分析（ANOVA） followed by Tukey 的事后检验来确定保护的统计学意义。
两次静脉免疫可产生 94%的抗蚊咬保护；皮内免疫产生 78%的保护，而皮内免疫加“胶带剥离”产生 94%的保护。静脉与皮内注射免疫的保护免疫程度无统计学差异。
使用微升注射器进行皮内注射可产生极佳的保护免疫。用大量辐射减毒的疟原虫孢子进行皮内免疫可产生与静脉免疫相当的保护免疫水平。尚待确定是否可以找到一种佐剂治疗方法，以在尽可能少的剂量下用尽可能少的减毒孢子来实现强烈的保护免疫，以便有可能扩展到人类免疫。
