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

通过了解疫苗诱导的保护与体液和细胞免疫反应的相关性来提高 FMD 疫苗的质量

基本信息

批准号：
BB/H009175/1
负责人：
Satya Parida
金额：
$ 111.19万
依托单位：
The Pirbright Institute
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2011
资助国家：
英国
起止时间：
2011 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FH009175%2F1
关键词：
Improving quality FMD vaccines understanding

项目摘要

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.

口蹄疫（Foot-and-mouth disease，FMD）是一种全球性分布的偶蹄类家畜和野生动物的高度接触性传染病。它在发展中国家，包括撒哈拉以南非洲和南亚的发展中国家仍然很普遍，在这些国家，它通过体重减轻、产奶量减少和丧失牵引力，严重影响牲畜的生产力。控制措施的成本以及对口蹄疫感染地区内和来自口蹄疫感染地区的动物及其产品贸易的限制，减少了农业产出和投资，从而大大加剧了这种损害。口蹄疫可以通过限制动物移动、屠宰受感染的动物和接种疫苗来控制;后者在疾病常见的国家持续使用，并在疾病新传入时作为紧急措施。口蹄疫病毒（FMDV）属于细小核糖核酸病毒科（Picornaviridae）口蹄疫病毒属（Aphthovirus）。它以7种免疫学上不同的类型（血清型）存在，它们之间很少或没有交叉保护。新的变异病毒周期性地出现，并且可能由于对相同血清型的现有亚型的免疫而难以控制。因此，疫苗株的要求根据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，必须谨慎选择疫苗。为了告知该选择过程，需要收集流行病毒并确定其与现有疫苗株的匹配，然后在必要时开发新的疫苗株。在发展中国家，使用在大细胞培养物中生长的灭活病毒进行疫苗接种对于控制口蹄疫至关重要，因为这些国家兽医服务薄弱，缺乏动物移动控制，无法依赖其他措施。然而，目前的疫苗仅提供短暂的保护（约6个月），其是种型特异性的，有时是菌株特异性的。每批疫苗还需要在动物身上进行口蹄疫病毒活攻毒试验，以确保疫苗的质量和效力。这需要昂贵的高防护设施，这些设施可能无法使用或存在病毒逃逸的风险。疫苗介导的口蹄疫控制方案面临的这些挑战导致发展中世界许多地区实际上放弃了建立口蹄疫监测和控制方案的尝试，并导致缺乏针对某些地区的疫苗株。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举措来实现。首先，将选择适合东非的疫苗株，并与这项工作相结合，简化选择疫苗株的方法，从而也为其他地区带来好处。第二，将评价已确定用于人用疫苗制剂并可增强疫苗诱导保护的效力和持续时间的新型佐剂用于FMD控制。第三，将开发和验证新的方法，以便能够根据对接种动物的免疫反应的分析对口蹄疫疫苗进行批量测试，而不需要用强毒活病毒攻击这些动物。结合使用新型佐剂以增加保护效力和持续时间，更好的疫苗匹配以诱导更有针对性的流行毒株覆盖，以及增加使用体外测定以降低疫苗测试成本，可以在疫苗使用的成本效益方面取得重大突破，从而在撒哈拉以南非洲和南亚控制口蹄疫。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Adenovirus Expressing Human Interferon Inhibits Replication of Foot and Mouth Disease Virus and Reduces Fatal Rate in Mice

表达人干扰素的腺病毒抑制口蹄疫病毒复制并降低小鼠死亡率

DOI：
10.4167/jbv.2012.42.3.224
发表时间：
2012
期刊：
Journal of Bacteriology and Virology
影响因子：
0
作者：
Chu J
通讯作者：
Chu J

Novel antibody binding determinants on the capsid surface of serotype O foot-and-mouth disease virus.

DOI：
10.1099/vir.0.060939-0
发表时间：
2014-05
期刊：
The Journal of general virology
影响因子：
0
作者：
Asfor AS;Upadhyaya S;Knowles NJ;King DP;Paton DJ;Mahapatra M
通讯作者：
Mahapatra M

Identification of Low- and High-Impact Hemagglutinin Amino Acid Substitutions That Drive Antigenic Drift of Influenza A(H1N1) Viruses.

DOI：
10.1371/journal.ppat.1005526
发表时间：
2016-04
期刊：
PLoS pathogens
影响因子：
6.7
作者：
Harvey WT;Benton DJ;Gregory V;Hall JP;Daniels RS;Bedford T;Haydon DT;Hay AJ;McCauley JW;Reeve R
通讯作者：
Reeve R

Genetic and antigenic characterisation of serotype A FMD viruses from East Africa to select new vaccine strains.

DOI：
10.1016/j.vaccine.2014.08.033
发表时间：
2014-10-07
期刊：
VACCINE
影响因子：
5.5
作者：
Bari, Fufa D.;Parida, Satya;Tekleghiorghis, Tesfaalem;Dekker, Aldo;Sangula, Abraham;Reeve, Richard;Haydon, Daniel T.;Paton, David J.;Mahapatra, Mana
通讯作者：
Mahapatra, Mana

Genetic Basis of Antigenic Variation of SAT3 Foot-And-Mouth Disease Viruses in Southern Africa.