Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, INSERM, CEA, Fontenay-aux-Roses, France.
School of Medical Sciences, Kirby Institute for Infection and Immunity, Cellular Genomics Futures Institute, University of New South Wales, Sydney, NSW, Australia.
Front Immunol. 2021 Mar 8;12:612747. doi: 10.3389/fimmu.2021.612747. eCollection 2021.
Most vaccines require multiple doses to induce long-lasting protective immunity in a high frequency of vaccines, and to ensure strong both individual and herd immunity. Repetitive immunogenic stimulations not only increase the intensity and durability of adaptive immunity, but also influence its quality. Several vaccine parameters are known to influence adaptive immune responses, including notably the number of immunizations, the delay between them, and the delivery sequence of different recombinant vaccine vectors. Furthermore, the initial effector innate immune response is key to activate and modulate B and T cell responses. Optimization of homologous and heterologous prime/boost vaccination strategies requires a thorough understanding of how vaccination history affects memory B and T cell characteristics. This requires deeper knowledge of how innate cells respond to multiple vaccine encounters. Here, we review how innate cells, more particularly those of the myeloid lineage, sense and respond differently to a 1st and a 2nd vaccine dose, both in an extrinsic and intrinsic manner. On one hand, the presence of primary specific antibodies and memory T cells, whose critical properties change with time after priming, provides a distinct environment for innate cells at the time of re-vaccination. On the other hand, innate cells themselves can exert enhanced intrinsic antimicrobial functions, long after initial stimulation, which is referred to as trained immunity. We discuss the potential of trained innate cells to be game-changers in prime/boost vaccine strategies. Their increased functionality in antigen uptake, antigen presentation, migration, and as cytokine producers, could indeed improve the restimulation of primary memory B and T cells and their differentiation into potent secondary memory cells in response to the boost. A better understanding of trained immunity mechanisms will be highly valuable for harnessing the full potential of trained innate cells, to optimize immunization strategies.
大多数疫苗需要多次接种才能在高频率的疫苗中诱导持久的保护性免疫，并确保个体和群体免疫力都很强。重复的免疫刺激不仅会增加适应性免疫的强度和持久性，还会影响其质量。有几个疫苗参数已知会影响适应性免疫反应，包括免疫接种的次数、接种之间的间隔以及不同重组疫苗载体的接种顺序。此外，初始效应性先天免疫反应对于激活和调节 B 细胞和 T 细胞反应至关重要。同源和异源初级/增强免疫接种策略的优化需要深入了解接种史如何影响记忆 B 和 T 细胞的特征。这需要更深入地了解先天细胞如何对多次疫苗接触做出反应。在这里，我们回顾了先天细胞，特别是髓系细胞，如何以外在和内在的方式不同地感知和响应第 1 次和第 2 次疫苗接种。一方面，初级特异性抗体和记忆 T 细胞的存在，其关键特性在初次免疫后随时间而变化，为再次接种时的先天细胞提供了一个独特的环境。另一方面，先天细胞本身可以在初次刺激后很长时间内发挥增强的内在抗菌功能，这被称为训练有素的免疫。我们讨论了训练有素的先天细胞在初级/增强疫苗策略中的潜在作用。它们在抗原摄取、抗原呈递、迁移和细胞因子产生方面的增强功能，确实可以改善对初级记忆 B 和 T 细胞的再刺激，并促进其分化为对增强剂有反应的有效次级记忆细胞。更好地了解训练有素的免疫机制对于充分利用训练有素的先天细胞潜力、优化免疫策略将具有很高的价值。
