Chlamydia trachomatis native major outer membrane protein induces partial protection in nonhuman primates: implication for a trachoma transmission-blocking vaccine.
Chlamydia trachomatis native major outer membrane protein induces partial protection in nonhuman primates: implication for a trachoma transmission-blocking vaccine.
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DOI：
10.4049/jimmunol.0804375
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发表时间：
2009-06-15
期刊：
影响因子：
--
通讯作者：
Caldwell HD
中科院分区：
文献类型：
--
作者：
Kari L;Whitmire WM;Crane DD;Reveneau N;Carlson JH;Goheen MM;Peterson EM;Pal S;de la Maza LM;Caldwell HD
疫苗可能是控制人类衣原体感染的最有效策略。最近的研究表明，用鼠衣原体主要外膜蛋白（MOMP）免疫小鼠，如果其天然三聚体结构被保留（nMOMP），则可以诱导显著的抗感染和疾病的保护作用。本研究的目的是在非人灵长类动物沙眼模型中研究沙眼衣原体nMOMP的免疫原性和疫苗效力。用nMOMP全身免疫食蟹猴（Macaca fascicularis），并对猴进行眼部攻毒。免疫诱导高血清IgG和伊加ELISA抗体滴度，抗体显示高菌株特异性中和活性。免疫猴的PBMC产生了广泛的交叉反应性，抗原特异性IFN-γ应答，相当于实验感染诱导的应答。免疫猴在早期排毒高峰期（第3-14天）表现出高度显著的感染负荷降低。然而，在随后的时间点，它们在感染负荷或感染持续时间方面与对照动物没有差异。免疫接种对眼部疾病的进展没有影响。这些结果表明，全身施用的nMOMP在非人灵长类动物中具有高度免疫原性，并对眼部衣原体攻击产生部分保护性免疫。这是第一次亚单位疫苗在非人灵长类动物中显示出明显的、显著的眼部脱落减少。部分保护性疫苗，特别是在儿童初次感染后显著降低感染负担的疫苗，可以中断自然的沙眼再感染周期。这可能对儿童和致敏成人之间的传播产生有益影响，这种传播会导致致盲性炎症疾病。
A vaccine is likely the most effective strategy for controlling human chlamydial infections. Recent studies have shown immunization with Chlamydia muridarum major outer membrane protein (MOMP) can induce significant protection against infection and disease in mice if its native trimeric structure is preserved (nMOMP). The objective of this study was to investigate the immunogenicity and vaccine efficacy of Chlamydia trachomatis nMOMP in a non-human primate trachoma model. Cynomolgus monkeys (Macaca fascicularis) were immunized systemically with nMOMP and monkeys were challenged ocularly. Immunization induced high serum IgG and IgA ELISA antibody titers, with antibodies displaying high strain-specific neutralizing activity. The PBMC of immunized monkeys produced a broadly cross-reactive, antigen-specific IFN-γ response equivalent to that induced by experimental infection. Immunized monkeys exhibited a highly significant decrease in infectious burden during the early peak shedding periods (days 3-14). However, at later time points they exhibited no difference from control animals in either burden or duration of infection. Immunization had no effect on the progression of ocular disease. These results show that systemically administered nMOMP is highly immunogenic in non-human primates and elicits partially protective immunity against ocular chlamydial challenge. This is the first time a subunit vaccine has shown a marked, significant reduction in ocular shedding in non-human primates. A partially protective vaccine, particularly one that significantly reduces infectious burden following primary infection of children, could interrupt the natural trachoma re-infection cycle. This could have a beneficial effect on the transmission between children and sensitized adults which drives blinding inflammatory disease.
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影响因子：
120.7
作者：
Chidambaram, JD;Alemayehu, W;Lietman, TM
通讯作者：
Lietman, TM
影响因子：
3.1
作者：
Pal, S;Theodor, I;delaMaza, LM
通讯作者：
delaMaza, LM
影响因子：
3.2
作者：
STEPHENS, RS;SANCHEZPESCADOR, R;URDEA, MS
通讯作者：
URDEA, MS
影响因子：
--
作者：
DAWSON, C;WOOD, TR;HANNA, L
通讯作者：
HANNA, L
影响因子：
158.5
作者：
SCHACHTER, J
通讯作者：
SCHACHTER, J