Liu Xiuping, Wetzler Lee M, Massari Paola
Evans BioMedical Research Center, Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, 650 Albany Street, Boston, MA 02118, USA.
Vaccine. 2008 Feb 6;26(6):786-96. doi: 10.1016/j.vaccine.2007.11.080. Epub 2007 Dec 26.
Porins from pathogenic Neisseriae are among several bacterial products with immune adjuvant activity. Neisseria meningitidis (Nme) PorB, has been shown to induce immune cells activation in a TLR2-dependent manner and acts as a vaccine immune adjuvant. The PorB porin from Neisseria lactamica (Nlac), a common nasopharyngeal commensal, shares significant structural and functional similarities with Nme PorB. In this work we ask whether the immune adjuvant ability of porins from pathogenic Neisserial strains is a characteristic shared with porins from non-pathogenic Neisserial species or whether it is unique for bacterial products derived from microorganisms capable of inducing inflammation and disease. We evaluated the potential immune adjuvant effect of Nlac PorB in mice using ovalbumin (OVA) as a prototype antigen. Immunization with Nlac PorB/OVA induced high OVA-specific IgG and IgM titers compared to OVA alone, similar to other adjuvants such as Nme PorB and alum. High titers of IgG1 and IgG2b were detected as well as production of IL-4, IL-10, IL-12 and INF-gamma in response to Nlac PorB, consistent with induction of both a Th1-type and a Th2-type immune response. OVA-specific proliferation was also determined in splenocytes from Nlac PorB/OVA-immunized mice. In addition, B cell activation in vitro and cytokine production in response to Nlac PorB was found to be mediated by TLR2, in a similar manner to Nme PorB.
致病性奈瑟菌的孔蛋白是几种具有免疫佐剂活性的细菌产物之一。脑膜炎奈瑟菌(Nme)的PorB已被证明以TLR2依赖性方式诱导免疫细胞活化,并作为疫苗免疫佐剂发挥作用。乳酸奈瑟菌(Nlac)是一种常见的鼻咽共生菌,其PorB孔蛋白与Nme PorB在结构和功能上有显著相似性。在这项研究中,我们探讨致病性奈瑟菌菌株的孔蛋白的免疫佐剂能力是与非致病性奈瑟菌物种的孔蛋白共有的特征,还是仅为能够诱导炎症和疾病的微生物衍生的细菌产物所特有。我们以卵清蛋白(OVA)作为原型抗原,评估了Nlac PorB在小鼠中的潜在免疫佐剂作用。与单独使用OVA相比,用Nlac PorB/OVA免疫诱导了高OVA特异性IgG和IgM滴度,类似于其他佐剂如Nme PorB和明矾。检测到高滴度的IgG1和IgG2b以及对Nlac PorB产生的IL-4、IL-10、IL-12和INF-γ ,这与Th1型和Th2型免疫反应的诱导一致也测定了来自Nlac PorB/OVA免疫小鼠的脾细胞中OVA特异性增殖。此外,发现体外B细胞活化和对Nlac PorB的细胞因子产生由TLR2介导,方式与Nme PorB相似。