Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas (CIDIE), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)/Universidad Católica de Córdoba (UCC), Córdoba, X5016DHK, Argentina.
Facultad de Ciencias de la Salud, Universidad Católica de Córdoba (UCC), Córdoba, X5004ASK, Argentina.
Nat Commun. 2019 Jan 21;10(1):361. doi: 10.1038/s41467-018-08265-9.
Intestinal and free-living protozoa, such as Giardia lamblia, express a dense coat of variant-specific surface proteins (VSPs) on trophozoites that protects the parasite inside the host's intestine. Here we show that VSPs not only are resistant to proteolytic digestion and extreme pH and temperatures but also stimulate host innate immune responses in a TLR-4 dependent manner. We show that these properties can be exploited to both protect and adjuvant vaccine antigens for oral administration. Chimeric Virus-like Particles (VLPs) decorated with VSPs and expressing model surface antigens, such as influenza virus hemagglutinin (HA) and neuraminidase (NA), are protected from degradation and activate antigen presenting cells in vitro. Orally administered VSP-pseudotyped VLPs, but not plain VLPs, generate robust immune responses that protect mice from influenza infection and HA-expressing tumors. This versatile vaccine platform has the attributes to meet the ultimate challenge of generating safe, stable and efficient oral vaccines.
肠道和自由生活的原生动物，如蓝氏贾第鞭毛虫，在滋养体上表达密集的变异特异性表面蛋白（VSP），保护寄生虫在宿主肠道内。在这里，我们表明 VSP 不仅能抵抗蛋白水解消化和极端 pH 值和温度，还能以 TLR-4 依赖的方式刺激宿主先天免疫反应。我们表明，这些特性可被用于口服保护和佐剂疫苗抗原。用 VSP 修饰的嵌合病毒样颗粒（VLPs）并表达模型表面抗原，如流感病毒血凝素（HA）和神经氨酸酶（NA），可以防止降解并在体外激活抗原呈递细胞。口服给予 VSP 假型 VLPs，但不是普通 VLPs，可产生强大的免疫反应，保护小鼠免受流感感染和表达 HA 的肿瘤的侵害。这种多功能疫苗平台具有满足生成安全、稳定和有效的口服疫苗的最终挑战的属性。
