Redman T K, Harmon C C, Michalek S M
Department of Microbiology, University of Alabama at Birmingham 35294-2170, USA.
Vaccine. 1996 Jun;14(9):868-78. doi: 10.1016/0264-410x(96)00013-8.
Recombinant strains of Salmonella typhimurium have been studied as antigen delivery systems to determine their effectiveness as multivalent vaccines. Here we compare the efficacy of two strains of S. typhimurium. chi 4072 (pYA2905) and chi 3987 (pYA2905), expressing SpaA of Streptococcus sobrinus 6715 as oral vaccines for dental caries. Both strains are attenuated delta cya delta crp delta asd mutants with their Asd phenotypes complemented by the Asd+ plasmid pYA2905, which also encodes a peptide fragment of SpaA. S. typhimurium chi 3987 (pYA2905), unlike S. typhimurium chi 4072 (pYA2905), contains the 100 kb S. typhimurium virulence plasmid. Fischer rats were orally immunized with approximately 10(9) S. typhimurium chi 3987 (pYA2905) or chi 4072 (pYA2905) and then challenged with cariogenic S. sobrinus 6715. Rats orally immunized with either strain of recombinant Salmonella developed salivary IgA anti-SpaA responses and had lower levels of S. sobrinus-induced dental caries than nonimmunized, infected animals. In a second series of experiments, the kinetics and isotype of the serum and salivary antibody responses were determined in rats orally immunized with S. typhimurium chi 3987 (pYA2905) or chi 4072 (pYA2905) on weeks 0 and 8. IgG and IgM serum antibody responses to SpaA and S. typhimurium were detected after the primary and secondary immunizations, and the secondary immunization boosted serum IgG anti-Salmonella activity. In general, animals immunized with chi 3987 (pYA2905) had higher serum anti-SpaA, as well as serum and salivary anti-Salmonella, responses than animals immunized with chi 4072 (pYA2905). This study demonstrates the effective use of two recombinant S. typhimurium strains as oral vaccines for inducing protective and sustained immune responses against a mucosal pathogen and suggests that the recombinant Salmonella vaccine strain carrying the virulence plasmid induced similar or higher protective immune responses than the strain lacking the virulence plasmid.
鼠伤寒沙门氏菌的重组菌株已作为抗原递送系统进行研究，以确定其作为多价疫苗的有效性。在此，我们比较了两种鼠伤寒沙门氏菌菌株chi 4072 (pYA2905)和chi 3987 (pYA2905)作为龋齿口服疫苗表达远缘链球菌6715的SpaA的效力。两种菌株均为减毒的ΔcyaΔcrpΔasd突变体，其Asd表型由Asd+质粒pYA2905互补，该质粒还编码SpaA的一个肽段。与chi 4072 (pYA2905)不同，chi 3987 (pYA2905)含有100 kb的鼠伤寒沙门氏菌毒力质粒。用约10⁹的chi 3987 (pYA2905)或chi 4072 (pYA290)对Fischer大鼠进行口服免疫，然后用致龋的远缘链球菌6715进行攻击。用任一重组沙门氏菌菌株口服免疫的大鼠均产生了唾液IgA抗SpaA反应，且与未免疫、受感染的动物相比，远缘链球菌诱导的龋齿水平较低。在第二系列实验中，在第0周和第8周用chi 3987 (pYA2905)或chi 4072 (pYA2905)对大鼠进行口服免疫，测定血清和唾液抗体反应的动力学和亚型。在初次和二次免疫后检测到针对SpaA和鼠伤寒沙门氏菌的IgG和IgM血清抗体反应，二次免疫增强了血清IgG抗沙门氏菌活性。一般来说，用chi 3987 (pYA2905)免疫的动物比用chi 4072 (pYA2905)免疫的动物具有更高的血清抗SpaA以及血清和唾液抗沙门氏菌反应。本研究证明了两种重组鼠伤寒沙门氏菌菌株作为口服疫苗可有效诱导针对黏膜病原体的保护性和持续性免疫反应，并表明携带毒力质粒的重组沙门氏菌疫苗株比缺乏毒力质粒的菌株诱导的保护性免疫反应相似或更高。
