Sun Guifeng, Pal Sukumar, Weiland Joseph, Peterson Ellena M, de la Maza Luis M
Department of Pathology and Laboratory Medicine, Medical Sciences, Room D440, University of California, Irvine, CA 92697-4800, United States.
Vaccine. 2009 Aug 6;27(36):5020-5. doi: 10.1016/j.vaccine.2009.05.008. Epub 2009 May 27.
To compare the ability of a native and a recombinant preparation of the major outer membrane protein of Chlamydia trachomatis mouse pneumonitis (MoPn; Ct-nMOMP and Ct-rMOMP) to protect against an intranasal (i.n.) challenge, BALB/c mice were vaccinated by the intramuscular (i.m.) and subcutaneous (s.c.) routes using CpG-1826 and Montanide ISA 720 as adjuvants. Animals inoculated i.n. with live elementary bodies (EB) of Chlamydia served as a positive control. Negative control groups were immunized with either Neisseria gonorrhoeae recombinant porin B (Ng-rPorB) or with minimal essential medium (MEM-0). Mice immunized with Ct-rMOMP, Ct-nMOMP and EB developed a strong immune response as shown by high levels of Chlamydia specific antibodies in serum and a strong T-cell lymphoproliferative response. Following the i.n. challenge with 10(4) inclusion forming units (IFU) of C. trachomatis, mice immunized with Ct-nMOMP or Ct-rMOMP lost significantly less weight than the negative control animals immunized with Ng-rPorB or MEM-0 (P<0.05). However, mice vaccinated with the Ct-nMOMP lost less weight than those immunized with the Ct-rMOMP (P<0.05). Mice were euthanized at 10 days following the challenge, their lungs weighed and the number of IFU of Chlamydia determined. Based on the lung weight and number of IFU recovered, significant protection was observed in the groups of mice immunized with both Ct-nMOMP and the Ct-rMOMP (P<0.05). Nevertheless, significantly better protection was achieved with the Ct-nMOMP in comparison with the Ct-rMOMP (P<0.05). In conclusion, vaccination with a preparation of the nMOMP elicited a more robust protection than immunization with rMOMP, suggesting that the conformational structure of MOMP is critical for inducing strong protection.
为比较沙眼衣原体鼠肺炎株(MoPn;Ct-nMOMP和Ct-rMOMP)主要外膜蛋白的天然制剂和重组制剂预防鼻内(i.n.)攻毒的能力,使用CpG-1826和Montanide ISA 720作为佐剂,通过肌肉内(i.m.)和皮下(s.c.)途径对BALB/c小鼠进行免疫接种。经鼻内接种沙眼衣原体活原体(EB)的动物作为阳性对照。阴性对照组用淋病奈瑟菌重组孔蛋白B(Ng-rPorB)或最低限度基本培养基(MEM-0)进行免疫。用Ct-rMOMP、Ct-nMOMP和EB免疫的小鼠产生了强烈的免疫反应,血清中沙眼衣原体特异性抗体水平高以及T细胞淋巴细胞增殖反应强烈表明了这一点。在用10⁴个沙眼衣原体包涵体形成单位(IFU)进行鼻内攻毒后,用Ct-nMOMP或Ct-rMOMP免疫的小鼠体重减轻明显少于用Ng-rPorB或MEM-0免疫的阴性对照动物(P<0.05)。然而,用Ct-nMOMP免疫的小鼠体重减轻少于用Ct-rMOMP免疫的小鼠(P<0.05)。攻毒后10天对小鼠实施安乐死,称量其肺重量并确定沙眼衣原体的IFU数量。基于回收的肺重量和IFU数量,在用Ct-nMOMP和Ct-rMOMP免疫的小鼠组中观察到显著的保护作用(P<0.05)。尽管如此,与Ct-rMOMP相比,Ct-nMOMP实现了显著更好的保护作用(P<0.05)。总之,用nMOMP制剂进行免疫接种比用rMOMP免疫引发了更强有力的保护作用,表明MOMP的构象结构对于诱导强大的保护作用至关重要。