Development of next generation vaccine technology inducing rapid and strong immunity through targeted delivery of antigens to chicken immune cells

开发下一代疫苗技术，通过将抗原定向递送至鸡免疫细胞，诱导快速而强大的免疫力

• 批准号: BB/T013087/1
• 负责人: Munir Iqbal
• 金额: $ 60.28万
• 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: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FT013087%2F1
• 关键词: Development; next; generation; vaccine; technology

Safe and disease-free poultry production systems are crucial for maintaining food supplies to feed the increasing human population and to improve the livelihoods of farming communities. However, the biggest threat in the sustainable growth of farmed animal production is the emergence, re-emergence and continual prevalence of a multitude of infectious animal pathogens, such as avian influenza. Primarily, the control against these pathogens is achieved through vaccination. However, the effectiveness of most of the current vaccines is suboptimal, where they may only reduce manifestation of clinical disease and mortality, but infected animals continue to shed viruses resulting in a continual chain of infections to susceptible naïve and vaccinated animals. For example, despite the large-scale deployment of multiple doses of influenza vaccine to an individual bird, manifestation of disease continues in the form of endemic prevalence and farmers continue to bear debilitating losses with up to 100 percent flock mortality or loss of egg production along with the threat of zoonotic infections. Therefore, improvement of the current vaccines are required that produce stronger immunity and full protection against disease, together with a reduction in shedding of infectious virus from infected animals, preventing the endemic prevalence of these viruses in farmed animals. In this proposal, we plan to develop robust and effective vaccines that elicit strong and durable humoral and cellular immune responses against viral pathogens which cause severe economic losses in poultry industries. As a proof-of-principle, we have demonstrated that targeted delivery of antigens to chicken immune cells potentiate the antigen-specific immune responses in vaccinated chickens compared to the untargeted counterpart or the conventional killed virus vaccines. The targeted vaccines demonstrated a significantly faster and a significantly higher immune response. These studies therefore provided strong data to take this new vaccine technology from laboratory to the farm. To achieve this goal, we have established partnership with a commercial poultry vaccine producer "MSD Animal Health". Through this collaboration, we will investigate how our developed targeted antigen delivery vaccine (TADV) formulation can further be optimised to i) induce even more rapid immunity and provide more potent and broader immune responses against antigenic AIV variants infecting poultry in different geographic regions; ii) enhance the production and delivery methods in chickens using our well-established insect cell cultures and recombinant viral vector (herpesvirus of turkey) system. The result obtained from this proposed research would provide a novel next generation improved AIV vaccine and a platform for improvement of vaccine technology against other important livestock and human pathogens. Availability of these novel highly protective and cost-effective disease control tools and strategies should minimise the impact of infectious diseases on farm animals, and offer substantial indirect economic, public health, environmental and social benefits to the UK and rest of the world.

安全和无病的家禽生产系统对于维持粮食供应以养活不断增加的人口和改善农业社区的生计至关重要。然而，养殖动物生产可持续增长的最大威胁是多种传染性动物病原体（如禽流感）的出现、重新出现和持续流行。首先，通过接种疫苗来控制这些病原体。然而，目前大多数疫苗的有效性是次优的，其中它们可能仅减少临床疾病的表现和死亡率，但受感染的动物继续散播病毒，导致易感的未接种和接种疫苗的动物的连续感染链。例如，尽管对单个禽类大规模部署了多剂量的流感疫苗，但疾病的表现仍以地方流行的形式继续，农民继续承受着高达100%的鸡群死亡率或产蛋损失的衰弱损失，沿着着人畜共患感染的威胁。因此，需要改进目前的疫苗，以产生更强的免疫力和对疾病的充分保护，同时减少感染性病毒从受感染动物的脱落，防止这些病毒在养殖动物中的地方流行。在这项提案中，我们计划开发强大而有效的疫苗，引发针对病毒病原体的强大而持久的体液和细胞免疫应答，这些病毒病原体在家禽业中造成严重的经济损失。作为原理证明，我们已经证明，与非靶向对应物或常规灭活病毒疫苗相比，将抗原靶向递送至鸡免疫细胞增强了接种鸡中的抗原特异性免疫应答。靶向疫苗表现出显著更快和显著更高的免疫应答。因此，这些研究提供了强有力的数据，将这种新的疫苗技术从实验室带到农场。为达致此目标，我们已与商业家禽疫苗生产商“默沙东动物保健”建立伙伴关系。通过这次合作，我们将研究如何进一步优化我们开发的靶向抗原递送疫苗（TADV）制剂，以i）诱导更快速的免疫，并提供针对感染不同地理区域家禽的抗原性AIV变体的更有效和更广泛的免疫应答; ii）使用我们成熟的昆虫细胞培养物和重组病毒载体，（土耳其疱疹病毒）系统。从这项拟议的研究中获得的结果将提供一种新的下一代改进的AIV疫苗，并为改进针对其他重要牲畜和人类病原体的疫苗技术提供一个平台。这些新型的高保护性和成本效益的疾病控制工具和策略的可用性应最大限度地减少传染病对农场动物的影响，并为英国和世界其他地区提供大量的间接经济，公共卫生，环境和社会效益。

项目成果

Antigenic Characterization of Human Monoclonal Antibodies for Therapeutic Use against H7N9 Avian Influenza Virus.

• DOI: 10.1128/jvi.01431-22
• 发表时间: 2023-01-31
• 期刊: Journal of virology
• 影响因子: 5.4