AVIRULENT SALMONELLA-TYPHIMURIUM DELTA-CYA DELTA-CRP ORAL VACCINE STRAINS EXPRESSING A STREPTOCOCCAL COLONIZATION AND VIRULENCE ANTIGEN
AVIRULENT SALMONELLA-TYPHIMURIUM DELTA-CYA DELTA-CRP ORAL VACCINE STRAINS EXPRESSING A STREPTOCOCCAL COLONIZATION AND VIRULENCE ANTIGEN
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DOI：
10.1016/s0264-410x(88)80020-3
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发表时间：
1988-04-01
期刊：
影响因子：
5.5
通讯作者：
KELLY, SM
中科院分区：
文献类型：
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作者：
CURTISS, R;GOLDSCHMIDT, RM;KELLY, SM
鼠伤寒沙门氏菌 SR-11 菌株由于 thecya 和 crp 基因的缺失 (Δ) 突变而分别缺乏腺苷酸环化酶和环 AMP 受体蛋白 (CRP)，对小鼠无毒力，并诱导高水平的保护性免疫，以抵抗随后野生型强毒株的攻击。鼠伤寒SR-11细胞。通过消除 100 kb 毒力质粒 pStSR100，这些 Δcya Δcrpm 突变体的无毒力得到增强，且不损害免疫原性。本报告证实了这些突变株的无毒力和免疫原性，证明四周龄和八周龄小鼠的免疫对体重增加没有不利影响，并且免疫力在初次免疫后持续至少九十天。无毒S.鼠伤寒菌株具有产生多种链球菌定植和毒力抗原的能力，用于构建重组二价口服疫苗菌株。远缘链球菌表面蛋白抗原 A (SpaA) 的重要抗原决定簇，推测是链球菌的关键定植抗原。 sobrinus，由Δcya Δcrp 鼠伤寒沙门氏菌菌株高水平表达。重组疫苗株在体外和动物体内都是稳定的（至少八天），它们定位于肠道相关淋巴组织（GALT）。
Salmonella typhimuriumSR-11 strains lacking adenylate cyclase and the cyclic AMP receptor protein (CRP) due to deletion (Δ) mutations in thecyaandcrpgenes, respectively, are avirulent for mice and induce high level protective immunity against subsequent challenge with wild-type virulentS. typhimuriumSR-11 cells. The avirulence of theseΔcya Δcrpmutants has been enhanced by elimination of the 100 kb virulence plasmid pStSR100 without impairing immunogenicity. The present report confirms the avirulence and immunogenicity of these mutant strains, demonstrates that immunization of both four- and eight-week-old mice has no adverse effect on weight gain, and that immunity lasts at least ninety days following initial immunization. AvirulentS. typhimuriumstrains have been endowed with the ability to produce several streptococcal colonization and virulence antigens for the purpose of constructing recombinant bivalent oral vaccine strains. Important antigenic determinants of theStreptococcus sobrinussurface protein antigen A (SpaA), presumed to be a critical colonization antigen ofS. sobrinus, are expressed at high level by theΔcya Δcrp S. typhimuriumstrains. The recombinant vaccine strains are stablein vitroand in animals (for a period of at least eight days) where they localize to the gut-associated lymphoid tissue (GALT).