The cornea is essential for vision yet highly sensitive to immune-mediated damage following infection. Generating vaccines that provide sterile immunity against ocular surface pathogens without evoking vision loss is therefore clinically challenging. Here, we tested a prophylactic live-attenuated vaccine against herpes simplex virus type 1 (HSV-1), a widespread human pathogen that can cause corneal blindness. Parenteral vaccination of mice resulted in sterile immunity to subsequent HSV-1 challenge in the cornea and suppressed productive infection of the nervous system. This protection was unmatched by a relevant glycoprotein subunit vaccine. Efficacy of the live-attenuated vaccine involved a T-dependent humoral immune response and complement C3 but not Fcγ-receptor 3 or interferon-α/β signaling. Proteomic analysis of viral proteins recognized by antiserum revealed an unexpected repertoire dominated by sequestered antigens rather than surface-exposed envelope glycoproteins. Ocular HSV-1 challenge in naive and subunit-vaccinated mice triggered vision loss and severe ocular pathologies including corneal opacification, scar formation, neovascularization, and sensation loss. However, corneal pathology was absent in mice receiving the live-attenuated vaccine concomitant with complete preservation of visual acuity. Collectively, this is the first comprehensive report of a prophylactic vaccine candidate that elicits resistance to ocular HSV-1 infection while fully preserving the cornea and visual acuity.

角膜对视力至关重要，但对感染后免疫介导的损伤高度敏感。因此，在不引起视力丧失的情况下产生针对眼表病原体提供无菌免疫的疫苗在临床上具有挑战性。在这里，我们测试了一种针对单纯疱疹病毒 1 型 (HSV-1) 的预防性减毒活疫苗，HSV-1 是一种广泛存在的人类病原体，可导致角膜失明。小鼠的肠胃外疫苗接种导致对角膜中随后的 HSV-1 攻击产生无菌免疫，并抑制神经系统的生产性感染。这种保护是相关糖蛋白亚单位疫苗无法比拟的。减毒活疫苗的功效涉及 T 依赖性体液免疫反应和补体 C3，但不涉及 Fcγ 受体 3 或干扰素-α/β 信号传导。抗血清识别的病毒蛋白的蛋白质组学分析揭示了一个意想不到的库，该库由隔离抗原而不是表面暴露的包膜糖蛋白主导。初次接种和亚单位疫苗接种小鼠的眼部 HSV-1 攻击引发视力丧失和严重的眼部病变，包括角膜混浊、疤痕形成、新生血管形成和感觉丧失。然而，在接受减毒活疫苗的小鼠中没有角膜病变，同时完全保留了视力。总的来说，这是第一份预防性候选疫苗的综合报告，该候选疫苗可在完全保护角膜和视力的同时引发对眼部 HSV-1 感染的抵抗力。初次接种和亚单位疫苗接种小鼠的眼部 HSV-1 攻击引发视力丧失和严重的眼部病变，包括角膜混浊、疤痕形成、新生血管形成和感觉丧失。然而，在接受减毒活疫苗的小鼠中没有角膜病变，同时完全保留了视力。总的来说，这是第一份预防性候选疫苗的综合报告，该候选疫苗可在完全保护角膜和视力的同时引发对眼部 HSV-1 感染的抵抗力。初次接种和亚单位疫苗接种小鼠的眼部 HSV-1 攻击引发视力丧失和严重的眼部病变，包括角膜混浊、疤痕形成、新生血管形成和感觉丧失。然而，在接受减毒活疫苗的小鼠中没有角膜病变，同时完全保留了视力。总的来说，这是第一份预防性候选疫苗的综合报告，该候选疫苗可在完全保护角膜和视力的同时引发对眼部 HSV-1 感染的抵抗力。