Contribution of immunological memory to protective immunity conferred by a Bacillus anthracis protective antigen-based vaccine
Contribution of immunological memory to protective immunity conferred by a Bacillus anthracis protective antigen-based vaccine
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DOI：
10.1128/iai.72.6.3471-3477.2004
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发表时间：
2004-06-01
影响因子：
3.1
通讯作者：
Reuveny, S
中科院分区：
文献类型：
--
作者：
Marcus, H;Danieli, R;Reuveny, S
以保护性抗原（PA）为基础的疫苗接种是对抗炭疽感染的有效措施。虽然由该疫苗引发的中和抗PA抗体滴度用作对抗炭疽的保护的良好相关性（S。M.P. D.白色，Y. Y.阿达尔，Y. Kafri，Z. Altboum，Y. Gozes，D. Kobiler，A. Shafferman和B。维兰感染Immun. 69：2888-2893，2001），没有关于PA自身的免疫记忆对保护作用的贡献的数据。因此，我们开发了一种豚鼠模型，在该模型中，用阈值水平的PA进行初次免疫可以诱导长期的T细胞免疫记忆应答，而不会诱导可检测到的抗PA抗体。具有相同阈值PA水平的致敏动物的再接种对于记忆激活是有效的，产生稳健且快速的次级应答。一个挑战与致死剂量（40 - 50%致死剂量，2,000孢子）的孢子后，加强疫苗接种表明，动物在第2，4和6天postboosting没有得到保护。仅从加强免疫后第8天起实现保护，同时检测循环中中和抗体滴度的保护水平。本文报道的研究的实际意义是，正如预期的那样，记忆的保护能力取决于用于初次免疫的PA剂量，并且当在炭疽芽孢杆菌孢子暴露之前致敏动物中不存在可检测的抗体时，用于炭疽的暴露后治疗的加强免疫的有效性可能非常有限。因此，为了在预期的疾病发作之前建立记忆依赖性保护，在暴露后情况下不应在没有伴随抗生素治疗的情况下使用加强免疫。
Protective antigen (PA)-based vaccination is an effective countermeasure to anthrax infection. While neutralizing anti-PA antibody titers elicited by this vaccine serve as good correlates for protection against anthrax (S. Reuveny, M. D. White, Y. Y. Adar, Y. Kafri, Z. Altboum, Y. Gozes, D. Kobiler, A. Shafferman, and B. Velan, Infect. Immun. 69:2888-2893, 2001), no data are available on the contribution of the immunological memory for PA itself to protection. We therefore developed a guinea pig model in which a primary immunization with threshold levels of PA can induce a long-term T-cell immunological memory response without inducing detectable anti-PA antibodies. A revaccination of primed animals with the same threshold PA levels was effective for memory activation, yielding a robust and rapid secondary response. A challenge with a lethal dose (40 50% lethal doses; 2,000 spores) of spores after the booster vaccinations indicated that animals were not protected at days 2, 4, and 6 postboosting. Protection was achieved only from the 8th day postboosting, concomitant with the detection of protective levels of neutralizing antibody titers in the circulation. The practical implications from the studies reported herein are that, as expected, the protective capacity of memory depends on the PA dose used for the primary immunization and that the effectiveness of booster immunizations for the postexposure treatment of anthrax may be very limited when no detectable antibodies are present in primed animals prior to Bacillus anthracis spore exposure. Therefore, to allow for the establishment of memory-dependent protection prior to the expected onset of disease, booster immunizations should not be used without concomitant antimicrobial treatment in postexposure scenarios.