Antibody signature of spontaneous clearance of Chlamydia trachomatis ocular infection and partial resistance against re-challenge in a nonhuman primate trachoma model.
Antibody signature of spontaneous clearance of Chlamydia trachomatis ocular infection and partial resistance against re-challenge in a nonhuman primate trachoma model.
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DOI：
10.1371/journal.pntd.0002248
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发表时间：
2013
影响因子：
3.8
通讯作者：
Caldwell HD
中科院分区：
文献类型：
--
作者：
Kari L;Bakios LE;Goheen MM;Bess LN;Watkins HS;Southern TR;Song L;Whitmire WM;Olivares-Zavaleta N;Caldwell HD
沙眼衣原体是沙眼的病原体，沙眼是世界上主要的传染性失明原因。在这里，我们调查是否在非人灵长类动物的原发感染的长期清除可归因于抗原变异或相关的衣原体抗原特异性的抗衣原体体液免疫反应的成熟。在整个长期原发性感染中分离的生物体的基因组测序显示，抗原变异与猴子无法有效解决其感染无关。为了探索体液免疫应答的成熟作为延迟清除的可能原因，使用在非变性条件下制备的固有放射性标记抗原通过放射免疫沉淀法分析血清。抗体识别仅限于抗原可变的主要外膜蛋白（MOMP）和一些抗原保守的抗原。MOMP的识别发生在感染后早期，与感染性眼部负担的减少相关，但与感染根除无关。与此相反，抗体识别的保守抗原，确定为PmpD，Hsp60，CPAF和Pgp 3，出现较晚，并与感染根除。对再激发的部分免疫与针对所有抗原的可辨别的抗体回忆应答相关。热处理破坏了PmpD和CPAF的抗体识别，而MOMP和Pgp 3受到部分影响，表明这些蛋白质上的构象表位特异性抗体可能对保护性免疫很重要。我们的研究结果表明，NHP中衣原体感染的延迟清除不是抗原变异的结果，而是衣原体逐渐成熟的结果。沙眼抗原特异性体液免疫应答。然而，我们不能得出结论，这些蛋白质的特异性抗体在宿主保护性免疫中发挥主要作用，因为它们可能是T细胞免疫的替代标志物。总的来说，我们的研究结果表明，一个有效的亚单位沙眼疫苗可能需要这些抗原在其天然构象的组合。 沙眼衣原体是沙眼的病原体，沙眼是世界上主要的传染性失明原因。在这项研究中，我们调查是否延迟清除的非人灵长类动物的原发感染是由于抗原变异或相关的衣原体抗原特异性体液免疫反应的逐渐变化。我们发现抗原变异与猴子无法有效解决感染无关。然而，探索免疫应答的变化作为延迟清除的可能原因显示，抗体识别仅限于抗原可变的主要表面蛋白和少数保守多肽。抗体识别的主要抗原可变的表面蛋白与感染负荷的最初减少，而保守的衣原体抗原的识别发生晚，与感染根除。这些研究结果表明，衣原体感染的延迟清除不是抗原变异的结果，而是对不同衣原体抗原的特异性体液免疫应答逐渐演变的结果。抗体识别至少部分针对构象表位，表明有效的亚单位沙眼疫苗可能需要以其天然构象递送的抗原组合。
Chlamydia trachomatis is the etiological agent of trachoma the world's leading cause of infectious blindness. Here, we investigate whether protracted clearance of a primary infection in nonhuman primates is attributable to antigenic variation or related to the maturation of the anti-chlamydial humoral immune response specific to chlamydial antigens. Genomic sequencing of organisms isolated throughout the protracted primary infection revealed that antigenic variation was not related to the inability of monkeys to efficiently resolve their infection. To explore the maturation of the humoral immune response as a possible reason for delayed clearance, sera were analyzed by radioimmunoprecipitation using intrinsically radio-labeled antigens prepared under non-denaturing conditions. Antibody recognition was restricted to the antigenically variable major outer membrane protein (MOMP) and a few antigenically conserved antigens. Recognition of MOMP occurred early post-infection and correlated with reduction in infectious ocular burdens but not with infection eradication. In contrast, antibody recognition of conserved antigens, identified as PmpD, Hsp60, CPAF and Pgp3, appeared late and correlated with infection eradication. Partial immunity to re-challenge was associated with a discernible antibody recall response against all antigens. Antibody recognition of PmpD and CPAF was destroyed by heat treatment while MOMP and Pgp3 were partially affected, indicating that antibody specific to conformational epitopes on these proteins may be important to protective immunity. Our findings suggest that delayed clearance of chlamydial infection in NHP is not the result of antigenic variation but rather a consequence of the gradual maturation of the C. trachomatis antigen-specific humoral immune response. However, we cannot conclude that antibodies specific for these proteins play the primary role in host protective immunity as they could be surrogate markers of T cell immunity. Collectively, our results argue that an efficacious subunit trachoma vaccine might require a combination of these antigens delivered in their native conformation. Chlamydia trachomatis is the etiological agent of trachoma the world's leading cause of infectious blindness. In this study, we investigated whether delayed clearance of a primary infection in nonhuman primates was attributable to antigenic variation or related to gradual changes in the humoral immune response specific to chlamydial antigens. We found that antigenic variation was not related to the inability of monkeys to efficiently resolve their infection. However, exploring changes in the immune response as a possible reason for delayed clearance revealed that antibody recognition was restricted to the antigenically variable major surface protein and a few conserved polypeptides. Antibody recognition of the major antigenically variable surface protein correlated with the initial reduction in infectious burdens while recognition of conserved chlamydial antigens occurred late and correlated with infection eradication. These findings suggest that delayed clearance of chlamydial infection is not the result of antigenic variation but a consequence of a gradually evolving humoral immune response specific to different chlamydial antigens. Antibody recognition was at least partially directed against conformational epitopes, indicating that an efficacious subunit trachoma vaccine might require a combination of antigens delivered in their native conformation.
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影响因子：
3.1
作者：
Murthy, Ashlesh K.;Chambers, James P.;Arulanandam, Bernard P.
通讯作者：
Arulanandam, Bernard P.
DOI：
10.1084/jem.20111266
发表时间：
2011-10-24
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kari L;Whitmire WM;Olivares-Zavaleta N;Goheen MM;Taylor LD;Carlson JH;Sturdevant GL;Lu C;Bakios LE;Randall LB;Parnell MJ;Zhong G;Caldwell HD
通讯作者：
Caldwell HD
影响因子：
3.1
作者：
COMANDUCCI, M;MANETTI, R;RATTI, G
通讯作者：
RATTI, G
影响因子：
158.5
作者：
SCHACHTER, J
通讯作者：
SCHACHTER, J
DOI：
10.4049/jimmunol.0804375
发表时间：
2009-06-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kari L;Whitmire WM;Crane DD;Reveneau N;Carlson JH;Goheen MM;Peterson EM;Pal S;de la Maza LM;Caldwell HD
通讯作者：
Caldwell HD