Improving the quality of FMD vaccines by understanding the correlation of vaccine-induced protection with humoral and cellular immune responses

口蹄疫是一种全球分布的偶蹄家畜和野生动物的高度传染性疾病。它在发展中国家仍然很普遍，包括撒哈拉以南非洲和南亚的发展中国家，在这些国家，它通过体重减轻、牛奶产量下降和风能损失严重影响牲畜生产力。控制措施的成本以及对口蹄疫疫区内外动物及其产品贸易的限制大大加剧了这种损害，减少了农业的产出和投资。口蹄疫可以通过限制动物活动、屠宰受影响的动物和接种疫苗来控制；后者在疾病常见的国家继续使用，并在新引入疾病时作为紧急措施。口蹄疫病毒(FMDV)属于口蹄疫病毒科口蹄疫病毒科口蹄疫病毒属。它以7种不同的免疫类型(血清型)存在，它们之间几乎没有交叉保护。新的变异病毒周期性地出现，可能对同一血清型的现有亚型的免疫力控制不佳。因此，疫苗株要求根据在不同地区流行或威胁不同地区的病毒类型和亚型而有所不同，疫苗的选择必须谨慎。要告知这一选择过程，需要收集正在传播的病毒并确定它们与现有疫苗株的匹配，然后在必要时开发新的疫苗株。使用在大细胞培养中生长的灭活病毒接种疫苗对于发展中国家的口蹄疫控制至关重要，在这些国家，兽医服务薄弱和缺乏对动物移动的控制，排除了对其他措施的依赖。然而，目前的疫苗只能提供短暂的保护(~6个月)，这种保护是特定于血清型的，有时也是特定于菌株的。每批疫苗还需要在有活口蹄疫病毒挑战的动物身上进行测试，以确保质量和效力。这需要昂贵的高遏制设施，这些设施可能不可用或构成病毒逃逸的风险。这些对疫苗介导的口蹄疫控制方案的挑战导致在发展中世界许多地区几乎放弃了建立口蹄疫监测和控制方案的尝试，并导致缺乏为某些地区量身定做的疫苗株。该项目力求克服上述制约因素，以便在发展中国家制定有效的疫苗控制战略。这将通过三项相辅相成的倡议来实现。首先，将选择适合东非的疫苗株，并与这项工作相关联，简化选择疫苗株的方法，也为其他地区带来好处。其次，将评估已被确定用于人类疫苗配方并可增强疫苗诱导保护的效力和持续时间的新型佐剂，以控制口蹄疫。第三，将开发和验证新的方法，使口蹄疫疫苗能够在分析接种动物的免疫反应的基础上进行批量测试，而不需要用毒力很强的活病毒挑战这些动物。结合使用新型佐剂以增加保护效力和持续时间，改进疫苗匹配以实现更有针对性的流行毒株覆盖，以及增加使用体外检测以降低疫苗测试成本，可在撒哈拉以南非洲和南亚在疫苗使用的成本效益方面取得重大突破，从而控制口蹄疫。

Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed domestic and wild animals with a global distribution. It remains widespread in developing countries including those of sub-Saharan Africa and South Asia, where it seriously affects livestock productivity through weight loss, decrease in milk yield and loss of draught power. This damage is greatly exacerbated by the cost of control measures and the restrictions imposed on the trade of animals and their products within and from FMD-infected areas reducing output and investment in agriculture. FMD can be controlled by restricting animal movements, by slaughtering affected animals and by vaccination; the latter being used continuously in countries where the disease is common and as an emergency measure if disease is newly introduced. FMD virus (FMDV) is in the genus Aphthovirus and the family Picornaviridae. It exists as 7 immunologically distinct types (serotypes) with little or no cross-protection between them. New variant viruses emerge periodically and may be poorly controlled by immunity to existing subtypes of the same serotype. Consequently, vaccine strain requirements differ according to the types and subtypes of virus prevailing in or threatening different regions and vaccines have to be selected with care. To inform this selection process requires collection of circulating viruses and determination of their match to existing vaccine strains, followed where necessary by development of new vaccine strains. Vaccination using killed virus grown in large cell cultures is critical to FMD control in developing countries where the weakness of veterinary services and lack of animal movement controls preclude reliance on other measures. However, current vaccines provide only short-lived protection (~6 months) that is serotype-specific and sometimes strain-specific. Each batch of the vaccine also needs to be tested in animals with live FMDV challenge to ensure quality and potency. This requires costly high containment facilities that may be unavailable or pose a risk of virus escape. These challenges to vaccine-mediated FMD control programmes have led to the virtual abandonment of attempts to establish FMD surveillance and control programmes in many parts of the developing world and to a lack of vaccine strains tailored for some regions. This project seeks to overcome the above-mentioned constraints to developing effective vaccine-based control strategies in developing countries. This will be achieved by three complementary initiatives. Firstly, vaccine strains will be selected that are appropriate for Eastern Africa, and associated to this work, the methodology for selecting vaccine strains will be simplified, bringing benefits to other regions as well. Secondly, novel adjuvants that have been identified for use in human vaccine formulations and that could enhance the potency and duration of vaccine-induced protection will be evaluated for FMD control. Thirdly, new methodology will be developed and validated to enable batch testing of FMD vaccines based on analysis of the immune responses of vaccinated animals, without a requirement to challenge these animals with virulent live virus. The combination of the use of novel adjuvants to increase the potency and duration of protection, better vaccine matching to induce more targeted coverage of circulating strains, and the increased use of in vitro assays to reduce the costs of vaccine testing could provide a significant breakthrough in the cost-effectiveness of vaccine use and hence FMD control in sub-Saharan Africa and South Asia.