Recent estimates suggest that one in two sexually active individuals will acquire a sexually transmitted infection by age 25, an alarming statistic that amounts to over 1 million new infections per day worldwide. Vaccination against STIs is highly desirable for alleviating this global burden of disease. Vaginal immunization is a promising strategy to combat transmission via the vaginal mucosa. The vagina is typically considered a poor inductive site for common correlates of adaptive immunity. However, emerging evidence suggests that immune tolerance may be overcome by precisely engineered vaccination schemes that orchestrate cell-mediated immunity and establish tissue resident memory immune cells. In this review, we will discuss the unique immunological milieu of the vaginal mucosa and our current understanding of correlates of pathogenesis and protection for several common STIs. We then present a summary of recent vaginal vaccine studies and explore the role that mucosal adjuvants and delivery systems play in enhancing protection according to requisite features of immunity. Finally, we offer perspectives on the challenges and future directions of vaginal vaccine delivery, discussing remaining physiological barriers and innovative vaccine formulations that may overcome them.

最近的估计表明，到 25 岁时，有二分之一的性活跃个体会感染性传播疾病，这是一个令人震惊的统计数据，全球每天新增感染人数超过 100 万。对于减轻这种全球疾病负担，非常需要接种 STI 疫苗。阴道免疫是对抗通过阴道黏膜传播的有前景的策略。阴道通常被认为是适应性免疫常见相关因素的不良诱导部位。然而，新出现的证据表明，免疫耐受可以通过精确设计的疫苗接种方案来克服，该方案可以协调细胞介导的免疫并建立组织驻留记忆免疫细胞。在本次审查中，我们将讨论阴道黏膜独特的免疫环境以及我们目前对几种常见性传播感染的发病机制和保护相关性的理解。然后，我们总结了最近的阴道疫苗研究，并根据免疫的必要特征探讨了粘膜佐剂和递送系统在增强保护中所起的作用。最后，我们就阴道疫苗递送的挑战和未来方向提出了看法，讨论了剩余的生理障碍和可能克服这些障碍的创新疫苗配方。