Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria, Australia.
PLoS One. 2010 Oct 26;5(10):e13622. doi: 10.1371/journal.pone.0013622.
Despite the availability of specific vaccines and antiviral drugs, influenza continues to impose a heavy toll on human health worldwide. Passive transfer of specific antibody (Ab) may provide a useful means of preventing or treating disease in unvaccinated individuals or those failing to adequately seroconvert, especially now that resistance to antiviral drugs is on the rise. However, preparation of appropriate Ab in large scale, quickly and on a yearly basis is viewed as a significant logistical hurdle for this approach to control seasonal influenza.
METHODOLOGY/PRINCIPAL FINDINGS: In this study, bovine colostrum, which contains approximately 500 g of IgG per milking per animal, has been investigated as a source of polyclonal antibody for delivery to the respiratory tract. IgG and F(ab')2 were purified from the hyperimmune colostrum of cows vaccinated with influenza A/Puerto Rico/8/34 (PR8) vaccine and were shown to have high hemagglutination-inhibitory and virus-neutralizing titers. In BALB/c mice, a single administration of either IgG or F(ab')2 could prevent the establishment of infection with a sublethal dose of PR8 virus when given as early as 7 days prior to exposure to virus. Pre-treated mice also survived an otherwise lethal dose of virus, the IgG- but not the F(ab')2-treated mice showing no weight loss. Successful reduction of established infection with this highly virulent virus was also observed with a single treatment 24 hr after virus exposure.
CONCLUSIONS/SIGNIFICANCE: These data suggest that a novel and commercially-scalable technique for preparing Ab from hyperimmune bovine colostrum could allow production of a valuable substitute for antiviral drugs to control influenza with the advantage of eliminating the need for daily administration.
尽管有特定的疫苗和抗病毒药物可用,但流感仍在全球范围内对人类健康造成严重威胁。特异性抗体(Ab)的被动转移可能是预防或治疗未接种疫苗个体或未能充分产生血清转化个体疾病的有用手段,尤其是在抗病毒药物耐药性不断上升的情况下。然而,每年大规模、快速地制备适当的 Ab 被认为是控制季节性流感的这种方法的一个重大后勤障碍。
方法/主要发现:在这项研究中,牛初乳被用作向呼吸道输送多克隆抗体的来源,牛初乳每头动物每次挤奶含有约 500 克 IgG。从接种流感 A/Puerto Rico/8/34(PR8)疫苗的奶牛的高免疫初乳中纯化了 IgG 和 F(ab')2,并显示出高血凝抑制和病毒中和效价。在 BALB/c 小鼠中,早在接触病毒前 7 天给予 IgG 或 F(ab')2 中的任何一种,均可预防亚致死剂量的 PR8 病毒感染的建立。预先处理的小鼠也能存活致命剂量的病毒,而 IgG 处理的小鼠(而非 F(ab')2 处理的小鼠)没有体重减轻。在接触病毒后 24 小时进行单次治疗也成功地减少了这种高致病性病毒的已建立感染。
结论/意义:这些数据表明,从高免疫牛初乳制备 Ab 的一种新的商业上可扩展技术可能允许生产一种有价值的抗病毒药物替代品来控制流感,其优势在于消除了每日给药的需要。