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首页> 外文期刊>Infection and immunity >Contribution of Immunological Memory to Protective Immunity Conferred by a Bacillus anthracis Protective Antigen-Based Vaccine
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Contribution of Immunological Memory to Protective Immunity Conferred by a Bacillus anthracis Protective Antigen-Based Vaccine

机译：免疫记忆对炭疽芽孢杆菌基于保护性抗原的疫苗所赋予的保护性免疫的贡献

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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.
机译：基于保护性抗原（PA）的疫苗接种是炭疽感染的有效对策。虽然由该疫苗引起的中和性抗PA抗体效价可作为抗炭疽的良好相关性（S.Reuveny，MD White，YY Adar，Y.Kafri，Z.Altboum，Y.Gozes，D.Kobiler，A.Shafferman，和B. Velan，《感染免疫》，> 69： 2888-2893，2001），尚无有关PA自身免疫记忆对保护作用的数据。因此，我们开发了一种豚鼠模型，其中用PA的阈值水平进行的初次免疫可以诱导长期的T细胞免疫记忆反应，而不诱导可检测的抗PA抗体。用相同的阈值PA水平重新接种致敏动物可有效激活记忆，从而产生强大而快速的继发反应。加强接种后，用致死剂量（40 50％致死剂量; 2,000孢子）的孢子进行攻击表明，在加强后第2、4和6天动物没有受到保护。仅在加强后第8天才能实现保护，同时要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含义是，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，并且当没有可检测的抗体时，加强免疫在炭疽暴露后治疗中的有效性可能非常有限。在炭疽芽孢杆菌孢子暴露之前的致敏动物中存在。因此，为了在预期的疾病发作之前建立依赖记忆的保护，在暴露后的情况下，如果不进行抗菌治疗，则不应使用加强免疫。

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