Department of Medicine, New York University School of Medicine, New York, NY, United States.
Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, United States.
Front Immunol. 2022 Aug 26;13:959656. doi: 10.3389/fimmu.2022.959656. eCollection 2022.
Bacillus Calmette-Guerin (BCG) has been used as a vaccine against tuberculosis since 1921 and remains the only currently approved vaccine for this infection. The recent discovery that BCG protects against initial infection, and not just against progression from latent to active disease, has significant implications for ongoing research into the immune mechanisms that are relevant to generate a solid host defense against (Mtb). In this review, we first explore the different components of immunity that are augmented after BCG vaccination. Next, we summarize current efforts to improve the efficacy of BCG through the development of recombinant strains, heterologous prime-boost approaches and the deployment of non-traditional routes. These efforts have included the development of new recombinant BCG strains, and various strategies for expression of important antigens such as those deleted during the attenuation process or antigens that are present only in Mtb. BCG is typically administered the intradermal route, raising questions about whether this could account for its apparent failure to generate long-lasting immunological memory in the lungs and the inconsistent level of protection against pulmonary tuberculosis in adults. Recent years have seen a resurgence of interest in the mucosal and intravenous delivery routes as they have been shown to induce a better immune response both in the systemic and mucosal compartments. Finally, we discuss the potential benefits of the ability of BCG to confer trained immunity in a non-specific manner by broadly stimulating a host immunity resulting in a generalized survival benefit in neonates and the elderly, while potentially offering benefits for the control of new and emerging infectious diseases such as COVID-19. Given that BCG will likely continue to be widely used well into the future, it remains of critical importance to better understand the immune responses driven by it and how to leverage these for the design of improved vaccination strategies against tuberculosis.
卡介苗（BCG）自 1921 年以来一直被用作结核病疫苗，仍然是目前唯一批准用于该感染的疫苗。最近的发现表明，BCG 不仅可以预防潜伏性疾病向活动性疾病的进展，而且可以预防初始感染，这对正在进行的研究具有重要意义，这些研究涉及与产生针对结核分枝杆菌（Mtb）的坚实宿主防御相关的免疫机制。在这篇综述中，我们首先探讨了 BCG 接种后增强的不同免疫成分。接下来，我们总结了目前通过开发重组菌株、异源初免-加强免疫方法和利用非传统途径来提高 BCG 疗效的努力。这些努力包括开发新的重组 BCG 菌株，以及各种表达重要抗原的策略，例如在减毒过程中缺失的抗原或仅存在于 Mtb 中的抗原。BCG 通常通过皮内途径给药，这引发了一个问题，即这是否可以解释其在肺部未能产生持久免疫记忆的明显失败以及对成人肺结核保护水平的不一致。近年来，人们对粘膜和静脉内给药途径重新产生了兴趣，因为它们已被证明可以在全身和粘膜部位诱导更好的免疫反应。最后，我们讨论了 BCG 通过广泛刺激宿主免疫以非特异性方式赋予训练免疫的能力的潜在好处，从而在新生儿和老年人中产生普遍的生存益处，同时可能为控制新出现的传染病提供益处，例如 COVID-19。鉴于 BCG 在未来很长一段时间内可能会继续被广泛使用，因此了解它驱动的免疫反应以及如何利用这些反应来设计针对结核病的改良疫苗接种策略仍然至关重要。
