A T-cell response to a liver-stage Plasmodium antigen is not boosted by repeated sporozoite immunizations

Murphy S.C.; Kas A.; Stone B.C.Bevan M.J.

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A T-cell response to a liver-stage Plasmodium antigen is not boosted by repeated sporozoite immunizations

机译：A T-cell response to a liver-stage Plasmodium antigen is not boosted by repeated sporozoite immunizations

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Development of an antimalarial subunit vaccine inducing protective cytotoxicTlymphocyte(CTL)-mediatedimmunity could pavetheway formalariaeradication. Experimental immunization with sporozoites induces this type of protective response, but the extremely large number of proteins expressed by Plasmodium parasites has so far prohibited the identification of sufficient discrete T-cell antigens to develop subunit vaccines that produce sterile immunity. Here, using mice singly immunized with Plasmodium yoelii sporozoites and highthroughput screening, we identified a unique CTL response against the parasite ribosomalL3 protein. Unlike CTL responses to the circumsporozoite protein (CSP), the population of L3-specific CTLs was not expanded by multiple sporozoite immunizations. CSP is abundant in the sporozoite itself, whereas L3 expression does not increase until the liver stage. The response induced by a single immunization with sporozoites reduces the parasite load in the liver so greatly during subsequent immunizations that L3-specific responses are only generated during the primary exposure. Functional L3-specific CTLs can, however, be expanded by heterologousprime-boostregimens. Thus, although repeat sporozoite immunization expands responses topreformed antigens like CSP that are present in the sporozoite itself, this immunization strategy may not expand CTLs targeting parasite proteins that are synthesized later. Heterologous strategies may be needed to increase CTL responses across the entire spectrum of Plasmodium liver-stage proteins.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2013年第15期|6055-6060|共6页
作者
Murphy S.C.; Kas A.; Stone B.C.Bevan M.J.;
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作者单位

Department of Laboratory Medicine, University of Washington, Medical Center, Seattle, WA 98195, United States;

Benaroya Research Institute, Seattle, WA 98101, United States;

Department of Immunology, University of Washington, Seattle, WA 98195, United States;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Epitope; Vaccination;

A T-cell response to a liver-stage Plasmodium antigen is not boosted by repeated sporozoite immunizations

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