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未包囊化的芳香族氨基酸营养缺陷型猪链球菌突变体作为猪用减毒活疫苗的潜在用途。

Potential use of an unencapsulated and aromatic amino acid-auxotrophic Streptococcus suis mutant as a live attenuated vaccine in swine.

作者信息

Fittipaldi Nahuel, Harel Josée, D'Amours Benoit, Lacouture Sonia, Kobisch Marylène, Gottschalk Marcelo

机构信息

Groupe de Recherche sur les Maladies Infectieuses du Porc, Centre de Recherche en Infectiologie Porcine and Canadian Research Network on Swine Infectious Diseases, Faculté de Médecine Vétérinaire, Université de Montréal, St-Hyacinthe, Québec, Canada.

出版信息

Vaccine. 2007 May 4;25(18):3524-35. doi: 10.1016/j.vaccine.2007.01.084. Epub 2007 Jan 30.

DOI:10.1016/j.vaccine.2007.01.084
PMID:17296252
Abstract

Streptococcus suis is responsible for severe economic losses to the swine industry. Prevention of the diseases caused by this pathogen is hampered by the inability of available vaccines to generate a protective response in pigs. A non-virulent, aromatic amino acid-auxotrophic and unencapsulated mutant strain of S. suis was generated in this study and a preliminary evaluation of its protective capacities was conducted in swine. Deletion of the cognate promoter of the aro operon in S. suis virulent strain S735 resulted in the abolishment of the expression of the four members of the operon, aroA, aroK, pheA and orf10. The resulting mutant strain BD101 was auxotrophic for aromatic amino acids as demonstrated by its failure to grow in a chemically defined medium unless it was supplemented with these compounds. In addition, as a result of the deletion of the cognate promoter of the aro operon, mutant BD101 lost its encapsulated phenotype. A protection assay was performed by immunisation of pigs with live strain BD101. Vaccination resulted in minor clinical signs but did not substantially impair the growth of vaccinated animals. Immunisation of animals with live mutant BD101 induced a considerable antibody response against S. suis. Vaccinated pigs presented only minor clinical signs and a survival rate of 100%, while 57% of non-vaccinated animals died, after a challenge with the virulent parent strain S735. In order to prevent S. suis infections in swine, it may be useful to further evaluate strain BD101 as a vaccine candidate.

摘要

猪链球菌给养猪业造成了严重的经济损失。由于现有疫苗无法在猪体内产生保护性反应,因此预防这种病原体引起的疾病受到了阻碍。本研究构建了一种无毒、芳香族氨基酸营养缺陷型且无荚膜的猪链球菌突变株,并在猪身上对其保护能力进行了初步评估。在猪链球菌强毒株S735中删除aro操纵子的同源启动子,导致该操纵子的四个成员aroA、aroK、pheA和orf10的表达被消除。由此产生的突变株BD101对芳香族氨基酸营养缺陷,这表现为它在化学限定培养基中无法生长,除非添加这些化合物。此外,由于aro操纵子同源启动子的缺失,突变株BD101失去了其荚膜表型。通过用活菌株BD101免疫猪进行了保护试验。接种疫苗导致轻微的临床症状,但并未显著影响接种动物的生长。用活的突变株BD101免疫动物诱导了针对猪链球菌的显著抗体反应。接种疫苗的猪仅出现轻微临床症状,存活率为100%,而在用强毒亲本菌株S735攻击后,57%的未接种动物死亡。为了预防猪的猪链球菌感染,进一步评估菌株BD101作为候选疫苗可能是有用的。

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