Genomic tailoring of autogenous poultry vaccines to reduce Campylobacter from farm to fork.

IF 6.9 1区 医学 Q1 IMMUNOLOGY
Jessica K Calland, Maiju E Pesonen, Jai Mehat, Ben Pascoe, David J Haydon, Jose Lourenco, Barbara Lukasiewicz, Evangelos Mourkas, Matthew D Hitchings, Roberto M La Ragione, Philip Hammond, Timothy S Wallis, Jukka Corander, Samuel K Sheppard
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Abstract

Campylobacter is a leading cause of food-borne gastroenteritis worldwide, linked to the consumption of contaminated poultry meat. Targeting this pathogen at source, vaccines for poultry can provide short-term caecal reductions in Campylobacter numbers in the chicken intestine. However, this approach is unlikely to reduce Campylobacter in the food chain or human incidence. This is likely as vaccines typically target only a subset of the high genomic strain diversity circulating among chicken flocks, and rapid evolution diminishes vaccine efficacy over time. To address this, we used a genomic approach to develop a whole-cell autogenous vaccine targeting isolates harbouring genes linked to survival outside of the host. We hyper-immunised a whole major UK breeder farm to passively target offspring colonisation using maternally-derived antibody. Monitoring progeny, broiler flocks revealed a near-complete shift in the post-vaccination Campylobacter population with an ~50% reduction in isolates harbouring extra-intestinal survival genes and a significant reduction of Campylobacter cells surviving on the surface of meat. Based on these findings, we developed a logistic regression model that predicted that vaccine efficacy could be extended to target 65% of a population of clinically relevant strains. Immuno-manipulation of poultry microbiomes towards less harmful commensal isolates by competitive exclusion, has major potential for reducing pathogens in the food production chain.

Abstract Image

基因组定制自体禽类疫苗,减少从农场到餐桌的弯曲杆菌。
弯曲杆菌是全球食源性肠胃炎的主要病因,与食用受污染的禽肉有关。针对这种病原体的源头,家禽疫苗可以在短期内减少鸡肠中弯曲杆菌的数量。然而,这种方法不太可能减少食物链中的弯曲杆菌或人类发病率。这很可能是因为疫苗通常只针对鸡群中流行的高基因组菌株多样性中的一部分,而快速进化会随着时间的推移降低疫苗的效力。为了解决这个问题,我们采用基因组学方法开发了一种全细胞自体疫苗,针对携带与宿主外生存相关基因的分离株。我们对整个英国主要种鸡场进行了超免疫,利用母源抗体被动地针对后代的定植。对后代肉鸡群的监测显示,接种疫苗后弯曲杆菌种群发生了近乎完全的转变,携带肠外生存基因的分离株减少了约 50%,在肉类表面存活的弯曲杆菌细胞显著减少。基于这些发现,我们建立了一个逻辑回归模型,预测疫苗效力可扩展到针对65%的临床相关菌株。通过竞争性排斥对家禽微生物组进行免疫调节,使其趋向于危害较小的共生分离菌,这对于减少食品生产链中的病原体具有重大潜力。
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来源期刊
NPJ Vaccines
NPJ Vaccines Immunology and Microbiology-Immunology
CiteScore
11.90
自引率
4.30%
发文量
146
审稿时长
11 weeks
期刊介绍: Online-only and open access, npj Vaccines is dedicated to highlighting the most important scientific advances in vaccine research and development.
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