The sustainability of poultry meat and egg global production, paramount to respond the worldwide demand for food, is challenged by poultry enteric diseases such as coccidiosis and necrotic enteritis.
Poultry has become the major source of animal protein in many developed and low-and-middle income countries (LMIC). Poultry meat production has doubled or tripled in many LMIC in the past two decades; in consequence, measures that prevent losses will be of great importance for sustainability of the poultry industry. Vaccination and/or chemoprophylaxis is available for many relevant avian pathogens, but intensive systems and backyard flocks remain threatened by viral, bacterial and parasitic infections. In particular, enteric diseases are a major concern for the poultry industry since they compromise the economics of meat and egg production, reduce animal welfare and can be a significant source of zoonotic transmission to humans. For example, as the use of in-feed antibiotics has controlled necrotic enteritis caused by Clostridium perfringens (Gram-positive, spore-forming bacteria), this disease is re-emerging in the US poultry industry and potentially in other countries if ionophores are banned. Initial reports estimate an increase of NE costs from US$2 billion in 2000 to US$6 billion in 2015. Pre-disposing factors affecting the environment of the gastrointestinal tract are needed to create a favorable environment for C. perfringens to overgrow and cause necrotic enteritis. These factors include co-infection of other pathogens such as Eimeria spp., stress, immunosuppression and nutrition. Based on previous studies, we hypothesise that protection against a key pre-disposing factor (Eimeria tenella) combined with vaccination with protective necrotic enteritis antigens may provide a highly effective mechanism for control the disease in chickens.
We generated two prototype vaccines against Clostridium perfringens by transgenesis into Eimeria tenella parasites. Each Eimeria-vectoring prototype proved successful express of the selected C. perfringens antigen and showed non-affected reproductive capacity when orally administrated. Specific immune responses were raised against C. perfringens when prototypes were orally delivered to chickens. Efficacy (immunoprotection) of the prototypes when used as a vaccine was compared to other expression systems and methods for delivery including injection. Oral vaccination with the prototype vaccine was expected to generate a better response than an injected vaccine, as it directly targets the gut, which is where C. perfringens causing necrotic enteritis would naturally infect the chicken, improving local immune responses and simplifying the vaccine administration to chicken flocks comprised of large numbers of animals. The industry partner in the project, MSD Animal Health - largest producer of poultry vaccines worldwide -, evaluated efficacy of the prototypes in a well-established animal model for C. perfringens Challenge. Data from the different trials are informing further applications for commercialization of this potential new vaccine solution for poultry vaccine mass oral administration, which could be extended to other poultry diseases.
The team developing this project was supported by the Bloomsbury SET® during 2019-2021 and follow-on phase during 2021-2022. The funds allowed academics to establish a productive collaboration with the industry partner and there are plans for continuing this collaboration. With the Bloomsbury SET® financial support, researchers have been able to take their ideas from early basic technology research (‘Technology Readiness Level’ – TLR – 2) into technology demonstration using animal vaccination/challenge studies (TRL7).
The Bloomsbury SET® programme also created opportunities for dissemination of this project and knowledge transfer experience through the ‘Vaccines in combating infectious diseases & antimicrobial resistance’ symposium and the “Developing the Knowledge Exchange Ecosystem, Partnering with Industry” session.
This project aimed to develop a vaccine platform based on Eimeria parasites to protect chickens against pathogens of different origin. The first use to generate a prototype and evaluate a specific product against the re-emerging disease necrotic enteritis is expected to have future applications that could have a direct impact in human health by the targeting of zoonotic organisms that transfer disease from chickens to human, and which have importance in both high income and low-and-middle income countries (e.g. Campylobacter, Salmonella).
Francisco Olmo (LSHTM), Beth Bruton and Marielle Hulten (MSD Animal Health)