Campos M, Pal S, O'Brien T P, Taylor H R, Prendergast R A, Whittum-Hudson J A
Conselho Brasileiro de Oftalmologia, Sao Paulo, Brazil.
Invest Ophthalmol Vis Sci. 1995 Jul;36(8):1477-91.
As shown in infected humans and in animal models of chlamydial infection, the major outer membrane protein (MOMP) of Chlamydia trachomatis is immunogenically potent. The purpose of this investigation was to test in the cynomolgus monkey model of trachoma a new extract of MOMP as a candidate vaccine against ocular chlamydial infection.
The nonionic detergent octyl-beta-D glucopyranoside (OGP) was used to extract MOMP from purified C. trachomatis (serovar C) elementary bodies. Protective immunization with OGP-MOMP by mucosal and systemic routes was compared in the cynomolgus monkey model of trachoma. All control and immunized monkeys were challenged by topical application of infectious C. trachomatis to the conjunctivae 35 days after the initiation of immunization.
Immunization with OGP-extracted MOMP successfully induced chlamydia-specific local and systemic immunity to MOMP and to whole organism before challenge and early clearance of infection by systemically immunized monkeys. Although ocular disease was not significantly reduced in either immunized group compared to control animals, the lowest clinical and microbiologic disease scores developed in two animals in the mucosal group with the highest immunoglobulin A tear antibody titers at day 0 to 14, whereas higher tear and serum immunoglobulin G correlated with reduced disease in the systemically immunized group.
These data demonstrate that despite evidence of vigorous MOMP-specific and other chlamydia-specific serologic and cell-mediated immunity, as well as anamnestic serologic responses to chlamydia, vaccination with OGP-MOMP was only partially protective against chlamydial ocular disease. The partial protection correlated best with tear immunoglobulin A responses after mucosal immunization and with local and systemic immunoglobulin G responses after peripheral immunization, suggesting that alternative chlamydial antigens may have to be considered in future vaccine development to induce more effective protective immunity and that evaluation of efficacy must be appropriate to route of immunization.
如在衣原体感染的人类和动物模型中所示,沙眼衣原体的主要外膜蛋白(MOMP)具有很强的免疫原性。本研究的目的是在沙眼猕猴模型中测试一种新的MOMP提取物作为抗眼部衣原体感染候选疫苗的效果。
使用非离子去污剂辛基-β-D-吡喃葡萄糖苷(OGP)从纯化的沙眼衣原体(血清型C)原体中提取MOMP。在沙眼猕猴模型中比较了通过黏膜和全身途径用OGP-MOMP进行的保护性免疫。所有对照和免疫的猴子在免疫开始35天后通过向结膜局部应用感染性沙眼衣原体进行攻击。
用OGP提取的MOMP免疫成功诱导了衣原体特异性的局部和全身免疫,使其在攻击前对MOMP和整个生物体产生免疫,并使全身免疫的猴子早期清除感染。尽管与对照动物相比,两个免疫组的眼部疾病均未显著减轻,但黏膜组的两只动物在第0至14天的泪液免疫球蛋白A抗体滴度最高,其临床和微生物疾病评分最低,而全身免疫组中较高的泪液和血清免疫球蛋白G与疾病减轻相关。
这些数据表明,尽管有证据表明存在强烈的MOMP特异性和其他衣原体特异性血清学和细胞介导的免疫,以及对衣原体的回忆性血清学反应,但用OGP-MOMP疫苗仅对衣原体眼部疾病有部分保护作用。这种部分保护与黏膜免疫后的泪液免疫球蛋白A反应以及外周免疫后的局部和全身免疫球蛋白G反应最相关,这表明在未来的疫苗开发中可能必须考虑其他衣原体抗原以诱导更有效的保护性免疫,并且疗效评估必须适合免疫途径。