Effectiveness of a vaccine composed of heat-killed Candida albicans and a novel mucosal adjuvant, LT(R192G), against systemic candidiasis.
Effectiveness of a vaccine composed of heat-killed Candida albicans and a novel mucosal adjuvant, LT(R192G), against systemic candidiasis.
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由热灭活的白色念珠菌和新型粘膜佐剂 LT(R192G) 组成的疫苗对抗系统性念珠菌病的有效性。
DOI：
10.1128/iai.67.2.826-833.1999
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发表时间：
1999
影响因子：
3.1
通讯作者：
Clements,JD
中科院分区：
文献类型：
--
作者：
Cárdenas-Freytag,L;Cheng,E;Mayeux,P;Domer,JE;Clements,JD
The incidence of fungal infections caused by the opportunistic yeastCandida albicanshas increased significantly in recent years. The ability to vaccinate selected patients against the organism would be advantageous. In this paper we describe a potential anti-C. albicansvaccine consisting of heat-killedC. albicans(HK-CA) in combination with the novel mucosal adjuvant LT(R192G), a genetically detoxified form of the heat-labile toxin of enterotoxigenicEscherichia coli. Groups of male CBA/J mice were immunized intranasally on three occasions at weekly intervals with 2 × 107HK-CA per dose, alone or in conjunction with 10 μg of LT(R192G) per dose. Two weeks following the last application of antigen, some animals were challenged intravenously (i.v.) with 104, 105, or 106viableC. albicansto assess protection as measured by survival and/or culture. Some groups of animals were footpad tested withC. albicansmannan to assess delayed-type hypersensitivity (DTH), and all the animals were bled for antibody assays. In two independent studies, all the animals immunized with HK-CA plus LT(R192G) were able to eradicate 104C. albicanscompletely, as determined by kidney culture 4 weeks after challenge. Animals immunized with HK-CA only had reduced levels ofC. albicanscompared to the adjuvant or saline-only control. Greatly enhanced survival was observed when mice immunized with HK-CA plus LT(R192G) were challenged with 105liveC. albicansas well. Animals immunized with HK-CA plus LT(R192G) developed a significant DH response, while those given HK-CA alone developed only marginal DH responses. High immunoglobulin G (IgG) levels to cytoplasmic antigens developed in mice immunized with HK-CA plus LT(R192G), but they were found only after i.v. challenge. Addition of adjuvant shifted the antibody isotype production in i.v.-challenged animals to a response dominated by IgG2a. Clearly, intranasal immunization with killedC. albicansin conjunction with LT(R192G) afforded significant levels of protection. This novel approach offers new possibilities for the development of an effective vaccine against candidiasis for use in humans.
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