公开(公告)号：US20170049872A1

公开(公告)日：2017-02-23

申请号：US15308338

申请日：2015-04-22

Applicant: Arizona Board of Regents on behalf of Arizona State University

Inventor： Kenneth Roland ,  Roy Curtiss ,  Pawel Laniewski ,  Arindam Mitra

IPC: A61K39/112

CPC classification number: A61K39/0275 ,  A61K2039/522 ,  A61K2039/542 ,  A61K2039/552 ,  C07K14/315

Abstract: We constructed S. Gallinarum strains deleted for the global regulatory gene fur (FIG. 1) and evaluated their virulence and protective efficacy in Rhode Island Red chicks and Brown Leghorn layers. The fur deletion mutant was a virulent and, when delivered orally to chicks, elicited excellent protection against lethal S. Gallinarum challenge. We also examined the effect of a pmi mutant and a combination of fur deletions with mutations in the pmi and rfaH genes, which affect O-antigen synthesis, and ansB, whose product inhibits host T cell responses. The ΔAfur Δpmi and Δfur ΔansB double mutants were attenuated, but not protective when delivered orally to chicks. However, a Δpmi Δfur strain was substantially immunogenic when administrated intramuscularly. Altogether our results show that the fur gene is essential for virulence of S. Gallinarum and the fur mutant is effective as a live recombinant vaccine against fowl typhoid.

Abstract translation: 我们构建了全球调控基因毛皮（图1）删除的S. Gallinarum菌株，并评估了其在罗德岛红色雏鸡和Brown Leghorn层中的毒力和保护功效。 毛皮缺失突变体是一种有毒的，当向小鸡口服递送时，引起极好的保护，防止致死的S. Gallinarum挑战。 我们还检测了pmi突变体和毛皮缺失与PMi和rfaH基因突变的影响，影响O抗原合成，以及ansB，其产物抑制宿主T细胞应答。 ΔAfurΔpmi和ΔfurΔansB双突变体在口服给小鸡时减毒，但不保护。 然而，当肌内注射时，ΔpmiΔfur菌株基本上是免疫原性的。 总的来说，我们的研究结果表明，毛皮基因对于金黄色葡萄球菌的毒力是必需的，毛皮突变体作为针对禽类伤寒的活重组疫苗是有效的。