Barnard Dale L, Belnap David M, Azadi Parastoo, Heiss Christian, Snyder D Scott, Bock Susan C, Konowalchuk Thomas W
ADVS Department, Institute for Antiviral Research, Utah State University, Logan, Utah 84041, United States.
School of Biological Sciences and Department of Biochemistry, University of Utah, Salt Lake City, Utah 84112, United States.
Heliyon. 2022 Jul;8(7):e09887. doi: 10.1016/j.heliyon.2022.e09887. Epub 2022 Jul 6.
Galahad™ is a proanthocyanidin complexed with polysaccharides that inactivates viruses and indicates potential for an innovative approach to making protective vaccines. The polysaccharide portion of Galahad™ consists mainly of arabinan and arabinogalactan. In a seven-day toxicity study in rats, it was not toxic even when tested undiluted. Galahad™ inactivated a wide range of DNA and RNA viruses including adenoviruses, corona viruses such as SARS-CoV-2, and influenza viruses. Electron microscopy studies showed that exposure to Galahad™ caused extensive clumping of virions followed by lack of detection of virions after longer periods of exposure. Based on the viral inactivation data, the hypotheses tested is that Galahad™ inactivation of virus can be used to formulate a protective inactivated virus vaccine. To evaluate this hypothesis, infectious influenza A virus (H5N1, Duck/MN/1525/81) with a titer of 10 CCID/0.1 ml was exposed for 10 min to Galahad™. This treatment caused the infectious virus titer to be reduced to below detectable limits. The Galahad™ -inactivated influenza preparation without adjuvant or preservative was given to BALB/c mice using a variety of routes of administration and dosing regimens. The most protective route of administration and dosing regimen was when mice were given the vaccine twice intranasally, the second dose coming 14 days after the primary vaccine dose. All the mice receiving this vaccine regimen survived the virus challenge while only 20% of the mice receiving placebo survived. This suggests that a Galahad™-inactivated influenza virus vaccine can elicit a protective immune response even without the use of an adjuvant. This technology should be investigated further for its potential to make effective human vaccines.
加拉哈德™是一种与多糖复合的原花青素,它能使病毒失活,并显示出制造保护性疫苗的创新方法的潜力。加拉哈德™的多糖部分主要由阿拉伯聚糖和阿拉伯半乳聚糖组成。在对大鼠进行的为期七天的毒性研究中,即使未经稀释测试,它也没有毒性。加拉哈德™能使多种DNA和RNA病毒失活,包括腺病毒、诸如严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的冠状病毒以及流感病毒。电子显微镜研究表明,暴露于加拉哈德™会导致病毒粒子大量聚集,长时间暴露后则检测不到病毒粒子。基于病毒失活数据,所检验的假设是加拉哈德™对病毒的失活作用可用于制备保护性灭活病毒疫苗。为评估这一假设,将滴度为10 CCID/0.1 ml的甲型流感病毒(H5N1,鸭/明尼苏达/1525/81)与加拉哈德™接触10分钟。这种处理使感染性病毒滴度降至可检测极限以下。将不含佐剂或防腐剂的加拉哈德™灭活流感制剂通过多种给药途径和给药方案给予BALB/c小鼠。最具保护性的给药途径和给药方案是小鼠经鼻内接种疫苗两次,第二剂在初次疫苗接种后14天接种。所有接受该疫苗方案的小鼠在病毒攻击中存活,而接受安慰剂的小鼠只有20%存活。这表明加拉哈德™灭活流感病毒疫苗即使不使用佐剂也能引发保护性免疫反应。这项技术因其制造有效人类疫苗的潜力应进一步研究。