Department of Bacteriology, University of Wisconsin-Madison, Madison, WI 53706, USA.
Toxins (Basel). 2023 Sep 8;15(9):563. doi: 10.3390/toxins15090563.
Vaccines are one of the most effective strategies to prevent pathogen-induced illness in humans. The earliest vaccines were based on live inoculations with low doses of live or related pathogens, which carried a relatively high risk of developing the disease they were meant to prevent. The introduction of attenuated and killed pathogens as vaccines dramatically reduced these risks; however, attenuated live vaccines still carry a risk of reversion to a pathogenic strain capable of causing disease. This risk is completely eliminated with recombinant protein or subunit vaccines, which are atoxic and non-infectious. However, these vaccines require adjuvants and often significant optimization to induce robust T-cell responses and long-lasting immune memory. Some pathogens produce protein toxins that cause or contribute to disease. To protect against the effects of such toxins, chemically inactivated toxoid vaccines have been found to be effective. Toxoid vaccines are successfully used today at a global scale to protect against tetanus and diphtheria. Recent developments for toxoid vaccines are investigating the possibilities of utilizing recombinant protein toxins mutated to eliminate biologic activity instead of chemically inactivated toxins. Finally, one of the most contemporary approaches toward vaccine design utilizes messenger RNA (mRNA) as a vaccine candidate. This approach was used globally to protect against coronavirus disease during the COVID-19 pandemic that began in 2019, due to its advantages of quick production and scale-up, and effectiveness in eliciting a neutralizing antibody response. Nonetheless, mRNA vaccines require specialized storage and transport conditions, posing challenges for low- and middle-income countries. Among multiple available technologies for vaccine design and formulation, which technology is most appropriate? This review focuses on the considerable developments that have been made in utilizing diverse vaccine technologies with a focus on vaccines targeting bacterial toxins. We describe how advancements in vaccine technology, combined with a deeper understanding of pathogen-host interactions, offer exciting and promising avenues for the development of new and improved vaccines.
疫苗是预防病原体引起人类疾病的最有效策略之一。最早的疫苗是基于低剂量活病原体或相关病原体的活接种，这带来了相当高的发病风险。减毒和灭活病原体疫苗的引入极大地降低了这些风险；然而，减毒活疫苗仍然有恢复为能够引起疾病的致病性菌株的风险。重组蛋白或亚单位疫苗完全消除了这种风险，这些疫苗是无毒且非传染性的。然而，这些疫苗需要佐剂，并且通常需要进行大量优化，以诱导强大的 T 细胞反应和持久的免疫记忆。一些病原体产生的蛋白毒素会导致或促成疾病。为了防止这些毒素的影响，化学灭活类毒素疫苗已被证明是有效的。类毒素疫苗今天在全球范围内成功用于预防破伤风和白喉。类毒素疫苗的最新发展正在研究利用突变以消除生物学活性而不是化学灭活毒素的重组蛋白毒素的可能性。最后，疫苗设计的最现代方法之一是利用信使 RNA（mRNA）作为疫苗候选物。由于其快速生产和扩大规模的优势，以及在诱导中和抗体反应方面的有效性，这种方法在 2019 年开始的 COVID-19 大流行期间被全球用于预防冠状病毒病。然而，mRNA 疫苗需要特殊的储存和运输条件，这对中低收入国家构成了挑战。在疫苗设计和配方的多种可用技术中，哪种技术最合适？本文重点介绍了利用多种疫苗技术的重大进展，重点介绍了针对细菌毒素的疫苗。我们描述了疫苗技术的进步如何与对病原体-宿主相互作用的更深入了解相结合，为开发新的和改进的疫苗提供了令人兴奋和有前途的途径。
