Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Vaccine. 2010 Apr 9;28(17):2917-23. doi: 10.1016/j.vaccine.2010.02.055. Epub 2010 Feb 25.
Development of an effective vaccine against malaria remains a priority. However, a significant number of individuals living in tropical areas are also likely to be co-infected with helminths, which are known to adversely affect immune responses to a number of different existing vaccines. Here we compare the response to two prototype malaria vaccines: a transmission blocking DNA vaccine based on Pfs25, and a pre-erythrocytic malaria vaccine based on irradiated sporozoites in mice infected with the intestinal nematode Heligmosomoides polygyrus. Following primary immunization with Pfs25 DNA vaccine, levels of total IgG, as well as IgG1, IgG2a, IgG2b (all P=0.0002), and IgG3 (P=0.03) Pfs25 antibodies were significantly lower in H. polygyrus-infected mice versus worm-free controls. Similar results were observed even after two additional boosts, while clearance of worms with anthelmintic treatment 3 weeks prior to primary immunization significantly reversed the inhibitory effect of helminth infection. In contrast, helminth infection had no inhibitory effect on immunization with irradiated sporozoites. Mean anti-CSP antibody responses were similar between H. polygyrus-infected and worm-free control mice following immunization with a single dose (65,000 sporozoites) of live radiation attenuated (irradiated) Plasmodium yoelii sporozoites (17X, non-lethal strain), and protection upon sporozoite challenge was equivalent between groups. These results indicate that helminth infection may adversely affect certain anti-malarial vaccine strategies, and highlight the importance of these interactions for malaria vaccine development.
开发有效的疟疾疫苗仍然是当务之急。然而，生活在热带地区的许多人也可能同时感染蠕虫，已知蠕虫会对许多不同现有疫苗的免疫反应产生不利影响。在这里，我们比较了两种疟疾疫苗原型的反应：一种基于 Pfs25 的传播阻断 DNA 疫苗，以及一种基于感染肠道线虫旋毛虫的辐照子孢子的前红细胞疟疾疫苗。在初次接种 Pfs25 DNA 疫苗后，与无蠕虫对照相比，感染旋毛虫的小鼠中的总 IgG 以及 IgG1、IgG2a、IgG2b（均 P=0.0002）和 IgG3（P=0.03）Pfs25 抗体水平显着降低。即使在进行了另外两次加强免疫后，也观察到了类似的结果，而在初次免疫前 3 周用驱虫药清除蠕虫可显着逆转蠕虫感染的抑制作用。相比之下，旋毛虫感染对辐照子孢子的免疫没有抑制作用。用单剂量（65,000 个子孢子）活辐射减毒（辐照）约氏疟原虫子孢子（17X，非致死株）免疫后，感染旋毛虫的小鼠与无蠕虫对照之间的平均抗 CSP 抗体反应相似，而在子孢子挑战之间，各组的保护作用相当。这些结果表明，蠕虫感染可能会对某些抗疟疾疫苗策略产生不利影响，并强调了这些相互作用对疟疾疫苗开发的重要性。
