Weiss Shay, Kobiler David, Levy Haim, Marcus Hadar, Pass Avi, Rothschild Nili, Altboum Zeev
Department of Infectious Diseases, Israel Institute for Biological Research, P.O. Box 19, Ness-Ziona, Israel 74100.
Infect Immun. 2006 Jan;74(1):394-8. doi: 10.1128/IAI.74.1.394-398.2006.
Correlates between immunological parameters and protection against Bacillus anthracis infection in animals vaccinated with protective antigen (PA)-based vaccines could provide surrogate markers to evaluate the putative protective efficiency of immunization in humans. In previous studies we demonstrated that neutralizing antibody levels serve as correlates for protection in guinea pigs (S. Reuveny et al., Infect. Immun. 69:2888-2893, 2001; H. Marcus et al., Infect. Immun. 72:3471-3477, 2004). In this study we evaluated similar correlates for protection by active and passive immunization of New Zealand White rabbits. Full immunization and partial immunization were achieved by single and multiple injections of standard and diluted doses of a PA-based vaccine. Passive immunization was carried out by injection of immune sera from rabbits vaccinated with PA-based vaccine prior to challenge with B. anthracis spores. Immunized rabbits were challenged by intranasal spore instillation with one of two virulent strains (strains Vollum and ATCC 6605). The immune competence was estimated by measuring the level of total anti-PA antibodies, the neutralizing antibody titers, and the conferred protective immunity. The results indicate that total anti-PA antibody titers greater than 1 x 10(5) conferred protection, whereas lower titers (between 10(4) and 10(5)) provided partial protection but failed to predict protection. Neutralizing antibody titers between 500 and 800 provided partial protection, while titers higher than 1,000 conferred protection. In conclusion, this study emphasizes that regardless of the immunization regimen or the time of challenge, neutralizing antibody titers are better predictors of protection than total anti-PA titers.
在用基于保护性抗原（PA）的疫苗接种的动物中，免疫参数与抗炭疽芽孢杆菌感染的保护作用之间的相关性可为评估人类免疫接种的假定保护效率提供替代指标。在先前的研究中，我们证明中和抗体水平可作为豚鼠保护作用的相关指标（S. Reuveny等人，《感染与免疫》69:2888 - 2893，2001；H. Marcus等人，《感染与免疫》72:3471 - 3477，2004）。在本研究中，我们评估了新西兰白兔主动免疫和被动免疫后类似的保护作用相关指标。通过单次和多次注射标准剂量和稀释剂量的基于PA的疫苗实现完全免疫和部分免疫。被动免疫是在炭疽芽孢杆菌孢子攻击前，注射用基于PA的疫苗接种的兔子的免疫血清来进行的。用两种强毒株（Vollum株和ATCC 6605株）之一通过鼻内滴注孢子对免疫的兔子进行攻击。通过测量总抗PA抗体水平、中和抗体滴度和赋予的保护性免疫来评估免疫能力。结果表明，总抗PA抗体滴度大于1×10⁵可提供保护，而较低滴度（10⁴至10⁵之间）提供部分保护但无法预测保护作用。500至800之间的中和抗体滴度提供部分保护，而高于1000的滴度则赋予保护作用。总之，本研究强调，无论免疫方案或攻击时间如何，中和抗体滴度比总抗PA滴度更能预测保护作用。
