Sutton Philip, Doidge Christopher, Pinczower Gideon, Wilson John, Harbour Stacey, Swierczak Agnieszka, Lee Adrian
Centre for Animal Biotechnology, University of Melbourne, Melbourne, Victoria, Australia.
FEMS Immunol Med Microbiol. 2007 Jul;50(2):213-9. doi: 10.1111/j.1574-695X.2006.00206.x.
Several studies have explored the production and immunogenicity of HpaA as a potential protective antigen against Helicobacter pylori but little is known regarding its protective capabilities. We therefore evaluated the protective efficacy of recombinant HpaA (rHpaA) as a candidate vaccine antigen against H. pylori. To explore the impact of genetic diversity, inbred and outbred mice were prophylactically and therapeutically immunized with rHpaA adjuvanted with cholera toxin (CT). Prophylactic immunization induced a reduction in bacterial colonization in BALB/c and QS mice, but was ineffective in C57BL/6 mice, despite induction of antigen-specific antibodies. By contrast, therapeutic immunization was effective in all three strains of mice. Prophylactic immunization with CT-adjuvanted rHpaA was more effective when delivered via the nasal route than following intragastric delivery in BALB/c mice. However, HpaA-mediated protection was inferior to that induced by bacterial lysate. Hence, protective efficacy is inducible with vaccines containing HpaA, most relevantly shown in an outbred population of mice. The effectiveness of protection induced by HpaA antigen was influenced by host genetics and was less effective than lysate. HpaA therefore has potential for the development of effective immunization against H. pylori but this would probably entail the antigen to be one component of a multiantigenic vaccine.
多项研究探讨了幽门螺杆菌潜在保护性抗原HpaA的产生及其免疫原性,但对其保护能力了解甚少。因此,我们评估了重组HpaA(rHpaA)作为抗幽门螺杆菌候选疫苗抗原的保护效果。为探究基因多样性的影响,用霍乱毒素(CT)佐剂化的rHpaA对近交系和远交系小鼠进行预防性和治疗性免疫。预防性免疫使BALB/c和QS小鼠的细菌定植减少,但在C57BL/6小鼠中无效,尽管诱导了抗原特异性抗体。相比之下,治疗性免疫在所有三种品系的小鼠中均有效。在BALB/c小鼠中,经鼻途径给予CT佐剂化的rHpaA进行预防性免疫比经胃内给药更有效。然而,HpaA介导的保护作用不如细菌裂解物诱导的保护作用。因此,含HpaA的疫苗可诱导保护效果,在远交系小鼠群体中最为明显。HpaA抗原诱导的保护效果受宿主基因影响,且不如裂解物有效。因此,HpaA有开发有效抗幽门螺杆菌免疫制剂的潜力,但这可能需要该抗原成为多抗原疫苗的一个组成部分。