Host protective immunity against pathogenic Mycobacterium tuberculosis (Mtb) infection is variable and poorly understood. Both prior Mtb infection and BCG vaccination have been reported to confer some protection against subsequent infection and/or disease. However, the immune correlates of host protection with or without BCG vaccination remain poorly understood. Similarly, the host response to concomitant infection with mixed Mtb strains is unclear. In this study, we used the rabbit model to examine the host response to various infectious doses of virulent Mtb HN878 with and without prior BCG vaccination, as well as simultaneous infection with a mixture of two Mtb clinical isolates HN878 and CDC1551. We demonstrate that both the ability of host immunity to control pulmonary Mtb infection and the protective efficacy of BCG vaccination against the progression of Mtb infection to disease is dependent on the infectious inoculum. The host response to infection with mixed Mtb strains mirrors the differential responses seen during infection with each of the strains alone. The protective response mounted against a hyperimmunogenic Mtb strain has a limited impact on the control of disease caused by a hypervirulent strain. This preclinical study will aid in predicting the success of any vaccination strategy and in optimizing TB vaccines.

中文翻译：

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感染的临床菌株的接种量和性状定义了兔模型中针对结核分枝杆菌感染的保护水平。

宿主对病原性结核分枝杆菌的保护性免疫（mtb）感染是多变的，人们对其了解甚少。据报道，既往的Mtb感染和BCG疫苗接种都可以为以后的感染和/或疾病提供一定的保护。但是，对带有或不带有BCG疫苗的宿主保护的免疫相关性知之甚少。同样，宿主对混合Mtb菌株伴随感染的反应尚不清楚。在这项研究中，我们使用兔子模型检查了宿主对各种感染剂量的强毒Mtb HN878的反应，有无预先接种BCG疫苗，以及同时感染了两种Mtb临床分离株HN878和CDC1551。我们证明宿主免疫力控制肺部Mtb感染的能力和BCG疫苗对Mtb感染向疾病进展的保护作用均取决于感染性接种物。宿主对混合Mtb菌株感染的反应反映了在单独感染每种菌株的过程中看到的差异反应。针对高免疫原性Mtb菌株的保护性应答对由高毒力菌株引起的疾病控制的影响有限。这项临床前研究将有助于预测任何疫苗接种策略的成功以及优化结核病疫苗。针对高免疫原性Mtb菌株的保护性应答对由高毒力菌株引起的疾病控制的影响有限。这项临床前研究将有助于预测任何疫苗接种策略的成功以及优化结核病疫苗。针对高免疫原性Mtb菌株的保护性应答对由高毒力菌株引起的疾病控制的影响有限。这项临床前研究将有助于预测任何疫苗接种策略的成功以及优化结核病疫苗。