Stepkowski Stanislaw, Bekbolsynov Dulat, Oenick Jared, Brar Surina, Mierzejewska Beata, Rees Michael A, Ekwenna Obi
Department of Medical Microbiology and Immunology, University of Toledo, Toledo, OH 43614, USA.
Neurological Surgery, The University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA.
Vaccines (Basel). 2024 Aug 30;12(9):992. doi: 10.3390/vaccines12090992.
Since their conception with the smallpox vaccine, vaccines used worldwide have mitigated multiple pandemics, including the recent COVID-19 outbreak. Insightful studies have uncovered the complexities of different functional networks of CD4 T cells (T helper 1 (Th1); Th2, Th17) and CD8 T cells (T cytotoxic; Tc), as well as B cell (B, B, B and B) subsets, during the response to vaccination. Both T and B cell subsets form central, peripheral, and tissue-resident subsets during vaccination. It has also become apparent that each vaccination forms a network of T regulatory subsets, namely CD4+ CD25+ Foxp3 T regulatory (Treg) cells and interleukin-10 (IL-10)-producing CD4+ Foxp3 T regulatory 1 (Tr1), as well as many others, which shape the quality/quantity of vaccine-specific IgM, IgG, and IgA antibody production. These components are especially critical for immunocompromised patients, such as older individuals and allograft recipients, as their vaccination may be ineffective or less effective. This review focuses on considering how the pre- and post-vaccination Treg/Tr1 levels influence the vaccination efficacy. Experimental and clinical work has revealed that Treg/Tr1 involvement evokes different immune mechanisms in diminishing vaccine-induced cellular/humoral responses. Alternative steps may be considered to improve the vaccination response, such as increasing the dose, changing the delivery route, and/or repeated booster doses of vaccines. Vaccination may be combined with anti-CD25 (IL-2Rα chain) or anti-programmed cell death protein 1 (PD-1) monoclonal antibodies (mAb) to decrease the Tregs and boost the T/B cell immune response. All of these data and strategies for immunizations are presented and discussed, aiming to improve the efficacy of vaccination in humans and especially in immunocompromised and older individuals, as well as organ transplant patients.
自从天花疫苗问世以来，全球使用的疫苗已减轻了多种大流行疾病的影响，包括近期的新冠疫情。有见地的研究揭示了在疫苗接种反应过程中，CD4 T细胞（辅助性T细胞1（Th1）、Th2、Th17）和CD8 T细胞（细胞毒性T细胞；Tc）以及B细胞（B1、B2、B3和B4）亚群不同功能网络的复杂性。在疫苗接种过程中，T细胞和B细胞亚群均形成中枢、外周和组织驻留亚群。同样明显的是，每次疫苗接种都会形成一个T调节亚群网络，即CD4+ CD25+ Foxp3调节性T（Treg）细胞和产生白细胞介素-10（IL-10）的CD4+ Foxp3调节性T细胞1（Tr1），以及许多其他亚群，它们塑造了疫苗特异性IgM、IgG和IgA抗体产生的质量/数量。这些成分对免疫功能低下的患者尤为关键，如老年人和同种异体移植受者，因为他们接种疫苗可能无效或效果较差。本综述着重探讨接种疫苗前后Treg/Tr1水平如何影响疫苗接种效果。实验和临床研究表明，Treg/Tr1的参与在减弱疫苗诱导的细胞/体液反应中引发了不同的免疫机制。可以考虑采取其他措施来改善疫苗接种反应，如增加剂量、改变给药途径和/或重复接种加强剂量的疫苗。疫苗接种可与抗CD25（IL-2Rα链）或抗程序性细胞死亡蛋白1（PD-1）单克隆抗体（mAb）联合使用，以减少Treg并增强T/B细胞免疫反应。本文展示并讨论了所有这些免疫数据和策略，旨在提高人类尤其是免疫功能低下者、老年人以及器官移植患者疫苗接种的效果。
