Multivalent poultry vaccine development using Protein Glycan Coupling Technology.
Multivalent poultry vaccine development using Protein Glycan Coupling Technology.
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DOI：
10.1186/s12934-021-01682-4
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发表时间：
2021-10-02
影响因子：
6.4
通讯作者：
Glycoengineering of Veterinary Vaccines Consortium
中科院分区：
文献类型：
--
作者：
Mauri M;Sannasiddappa TH;Vohra P;Corona-Torres R;Smith AA;Chintoan-Uta C;Bremner A;Terra VS;Abouelhadid S;Stevens MP;Grant AJ;Cuccui J;Wren BW;Glycoengineering of Veterinary Vaccines Consortium
家禽是世界上最受欢迎的动物性食品，仅在过去20年中，全球产量就增加了两倍。低成本的疫苗，可以结合起来，以保护家禽免受多种感染是目前全球的当务之急。糖缀合物疫苗由与靶向病原体的聚糖抗原共价偶联的免疫原性蛋白质组成，在人类疫苗学中具有经证实的跟踪记录，但由于过高的制造成本而尚未用于牲畜。为了克服这一点，我们使用蛋白聚糖偶联技术（PGCT），该技术能够以显著降低的成本在细菌细胞中生产糖缀合物，以产生候选的基于聚糖的活疫苗，该活疫苗旨在同时保护免受空肠弯曲杆菌、禽致病性大肠杆菌（APEC）和产气荚膜梭菌的侵害。弯曲杆菌是食物中毒的最常见原因，而大肠杆菌病和坏死性肠炎是家禽中广泛和毁灭性的传染病。我们证明了C的功能转移。空肠蛋白糖基化（pgl）位点插入到APEC χ7122血清型O 78：H9的基因组中。经口接种鸡后，整合导致χ7122菌株轻度减毒，而不损害其定殖呼吸道的能力。我们利用χ7122 pgl整合子作为细菌载体，递送用C.空肠七糖聚糖抗原。为此，我们工程化了X7122 pgl以表达来自C.产气荚膜梭菌，并测试了其减少鸡盲肠定殖的能力。空肠和保护免受气囊内攻击同源APEC菌株。我们产生了一种基于聚糖的多价活疫苗候选物，其具有诱导针对关键禽类和人畜共患病病原体的保护的潜力（C。jejuni、APEC、C.产气荚膜杆菌）。活疫苗在测试条件下未能显著减少弯曲杆菌定殖，但对同源APEC攻击具有保护性。尽管如此，我们提出了一个战略，以生产低成本的“减毒活多价疫苗工厂”的能力，表达糖缀合物在家禽。在线版本包含补充材料，可通过10.1186/s12934-021-01682-4获得。
Poultry is the world's most popular animal-based food and global production has tripled in the past 20 years alone. Low-cost vaccines that can be combined to protect poultry against multiple infections are a current global imperative. Glycoconjugate vaccines, which consist of an immunogenic protein covalently coupled to glycan antigens of the targeted pathogen, have a proven track record in human vaccinology, but have yet to be used for livestock due to prohibitively high manufacturing costs. To overcome this, we use Protein Glycan Coupling Technology (PGCT), which enables the production of glycoconjugates in bacterial cells at considerably reduced costs, to generate a candidate glycan-based live vaccine intended to simultaneously protect against Campylobacter jejuni, avian pathogenic Escherichia coli (APEC) and Clostridium perfringens. Campylobacter is the most common cause of food poisoning, whereas colibacillosis and necrotic enteritis are widespread and devastating infectious diseases in poultry. We demonstrate the functional transfer of C. jejuni protein glycosylation (pgl) locus into the genome of APEC χ7122 serotype O78:H9. The integration caused mild attenuation of the χ7122 strain following oral inoculation of chickens without impairing its ability to colonise the respiratory tract. We exploit the χ7122 pgl integrant as bacterial vectors delivering a glycoprotein decorated with the C. jejuni heptasaccharide glycan antigen. To this end we engineered χ7122 pgl to express glycosylated NetB toxoid from C. perfringens and tested its ability to reduce caecal colonisation of chickens by C. jejuni and protect against intra-air sac challenge with the homologous APEC strain. We generated a candidate glycan-based multivalent live vaccine with the potential to induce protection against key avian and zoonotic pathogens (C. jejuni, APEC, C. perfringens). The live vaccine failed to significantly reduce Campylobacter colonisation under the conditions tested but was protective against homologous APEC challenge. Nevertheless, we present a strategy towards the production of low-cost “live-attenuated multivalent vaccine factories” with the ability to express glycoconjugates in poultry. The online version contains supplementary material available at 10.1186/s12934-021-01682-4.
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影响因子：
3.1
作者：
DONNENBERG, MS;KAPER, JB
通讯作者：
KAPER, JB
DOI：
10.1073/pnas.120163297
发表时间：
2000-06-06
影响因子：
11.1
作者：
Datsenko, KA;Wanner, BL
通讯作者：
Wanner, BL
影响因子：
3.5
作者：
Dykxhoorn, DM;StPierre, R;Linn, T
通讯作者：
Linn, T
影响因子：
7
作者：
Cain, Joel A.;Dale, Ashleigh L.;Cordwell, Stuart J.
通讯作者：
Cordwell, Stuart J.
影响因子：
3.1
作者：
Alemka, Abofu;Nothaft, Harald;Szymanski, Christine M.
通讯作者：
Szymanski, Christine M.