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表达多杀性巴氏杆菌 PlpE 蛋白的重组减毒猪霍乱沙门氏菌载体可保护小鼠免受致死性攻击。

Recombinant-attenuated Salmonella enterica serovar Choleraesuis vector expressing the PlpE protein of Pasteurella multocida protects mice from lethal challenge.

机构信息

College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, People's Republic of China.

Jiangsu Co-innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, China.

出版信息

BMC Vet Res. 2023 Aug 19;19(1):128. doi: 10.1186/s12917-023-03679-0.

Abstract

BACKGROUND

Bacterial surface proteins play key roles in pathogenicity and often contribute to microbial adhesion and invasion. Pasteurella lipoprotein E (PlpE), a Pasteurella multocida (P. multocida) surface protein, has recently been identified as a potential vaccine candidate. Live attenuated Salmonella strains have a number of potential advantages as vaccine vectors, including immunization with live vector can mimic natural infections by organisms, lead to the induction of mucosal, humoral, and cellular immune responses. In this study, a previously constructed recombinant attenuated Salmonella Choleraesuis (S. Choleraesuis) vector rSC0016 was used to synthesize and secrete the surface protein PlpE of P. multocida to form the vaccine candidate rSC0016(pS-PlpE). Subsequently, the immunogenicity of S. Choleraesuis rSC0016(pS-PlpE) as an oral vaccine to induce protective immunity against P. multocida in mice was evaluated.

RESULTS

After immunization, the recombinant attenuated S. Choleraesuis vector can efficiently delivered P. multocida PlpE protein in vivo and induced a specific immune response against this heterologous antigen in mice. In addition, compared with the inactivated vaccine, empty vector (rSC0016(pYA3493)) and PBS immunized groups, the rSC0016(pS-PlpE) vaccine candidate group induced higher antigen-specific mucosal, humoral and mixed Th1/Th2 cellular immune responses. After intraperitoneal challenge, the rSC0016(pS-PlpE) immunized group had a markedly enhanced survival rate (80%), a better protection efficiency than 60% of the inactivated vaccine group, and significantly reduced tissue damage.

CONCLUSIONS

In conclusion, our study found that the rSC0016(pS-PlpE) vaccine candidate provided good protection against challenge with wild-type P. multocida serotype A in a mouse infection model, and may potentially be considered for use as a universal vaccine against multiple serotypes of P. multocida in livestock, including pigs.

摘要

背景

细菌表面蛋白在致病性中起着关键作用,通常有助于微生物的黏附和入侵。巴氏杆菌脂蛋白 E(PlpE)是多杀巴斯德菌(P.multocida)表面蛋白,最近被确定为一种有潜力的疫苗候选物。减毒活沙门氏菌菌株作为疫苗载体具有许多潜在的优势,包括用活载体进行免疫可以模拟生物体的自然感染,导致黏膜、体液和细胞免疫反应的诱导。在本研究中,先前构建的重组减毒猪霍乱沙门氏菌(S.Choleraesuis)载体 rSC0016 被用于合成和分泌多杀巴斯德菌的表面蛋白 PlpE,形成疫苗候选物 rSC0016(pS-PlpE)。随后,评估了 S.Choleraesuis rSC0016(pS-PlpE)作为口服疫苗诱导小鼠对多杀巴斯德菌保护性免疫的免疫原性。

结果

免疫后,重组减毒 S.霍乱沙门氏菌载体可在体内有效传递多杀巴斯德菌 PlpE 蛋白,并在小鼠中诱导针对这种异源抗原的特异性免疫反应。此外,与灭活疫苗相比,空载体(rSC0016(pYA3493))和 PBS 免疫组,rSC0016(pS-PlpE)候选疫苗组诱导了更高的抗原特异性黏膜、体液和混合 Th1/Th2 细胞免疫反应。腹腔攻毒后,rSC0016(pS-PlpE)免疫组的存活率明显提高(80%),保护效率高于灭活疫苗组的 60%,且组织损伤明显减轻。

结论

综上所述,本研究发现 rSC0016(pS-PlpE)候选疫苗在小鼠感染模型中对野生型 A 型多杀巴斯德菌的攻击提供了良好的保护作用,可能被考虑用于预防包括猪在内的家畜多种多杀巴斯德菌血清型的通用疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/771b/10439597/27c9075755ee/12917_2023_3679_Fig1_HTML.jpg

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