Daniell Henry, Guo Yuwei, Singh Rahul, Karki Uddhab, Kulchar Rachel J, Wakade Geetanjali, Pihlava Juha-Matti, Khazaei Hamid, Cohen Gary H
Department of Basic & Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Basic & Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Mol Ther. 2025 Jan 8;33(1):184-200. doi: 10.1016/j.ymthe.2024.12.008. Epub 2024 Dec 10.
Lack of Herpes Simplex Virus (HSV) vaccine, low vaccination rates of Influenza viruses, waning immunity and viral transmission after vaccination underscore the need to reduce viral loads at their transmission sites. Oral virus transmission is several orders of magnitude higher than nasal transmission. Therefore, in this study, we evaluated neutralization of viruses using a natural viral trap protein (FRIL) formulated in clinical-grade chewing gum. FRIL is highly stable in the lablab bean powder (683 days) and in chewing gum (790 days), and fully functional (794 days) when stored at ambient temperature. They passed the bioburden test with no aerobic bacteria, yeasts/molds, with minimal moisture content (1.28-5.9%). Bean gum extracts trapped HSV-1/HSV-2 75-94% in a dose-dependent manner through virus self-aggregation. Mastication simulator released >50% release of FRIL within 15 min of chewing the bean gum. In plaque reduction assays, >95% neutralization of H1N1 and H3N2 required ∼40 mg/mL, HSV-1 160 mg/mL, and HSV-2 74 mg/mL of bean gum for 1,000 copies/mL virus particles. Therefore, a 2000 mg bean gum tablet has more than adequate potency for clinical evaluation and is safe with no detectable levels of glycosides. These observations augur well for evaluating bean gum in human clinical studies to minimize virus infection/transmission.
单纯疱疹病毒(HSV)疫苗的缺乏、流感病毒的低接种率、免疫力的减弱以及接种疫苗后的病毒传播,都凸显了在病毒传播部位降低病毒载量的必要性。口腔病毒传播比鼻腔传播高几个数量级。因此,在本研究中,我们评估了使用临床级口香糖中配制的天然病毒捕获蛋白(FRIL)对病毒的中和作用。FRIL在金甲豆粉(683天)和口香糖(790天)中高度稳定,在室温下储存时功能完全正常(794天)。它们通过了生物负荷测试,无需氧菌、酵母/霉菌,水分含量极低(1.28 - 5.9%)。金甲豆胶提取物通过病毒自聚集以剂量依赖方式捕获75 - 94%的HSV - 1/HSV - 2。咀嚼模拟器在咀嚼金甲豆胶15分钟内释放>50%的FRIL。在蚀斑减少试验中,对于1000拷贝/mL病毒颗粒,H1N1和H3N2的>95%中和需要约40mg/mL的金甲豆胶,HSV - 1需要160mg/mL,HSV - 2需要74mg/mL。因此,一片2000mg的金甲豆胶片剂具有足够的效力用于临床评估,并且安全,未检测到糖苷水平。这些观察结果对于在人体临床研究中评估金甲豆胶以尽量减少病毒感染/传播是个好兆头。