Bucarey Sergio A, Maldonado Lucy D, Duarte Francisco, Hidalgo Alejandro A, Sáenz Leonardo
Centro Biotecnológico Veterinario, Biovetec, Departamento de Ciencias Biológicas Animales, Facultad de Ciencias Veterinarias y Pecuarias, Universidad de Chile, Santa Rosa 11735, La Pintana, Santiago 8820808, Chile.
Escuela de Química y Farmacia, Facultad de Medicina, Universidad Andres Bello, Sazié 2320, Santiago 8370134, Chile.
Vaccines (Basel). 2024 Dec 12;12(12):1400. doi: 10.3390/vaccines12121400.
Immunization against Gonadotropin-Releasing Hormone (GnRH) has been successfully explored and developed for the parenteral inoculation of animals, aimed at controlling fertility, reducing male aggressiveness, and preventing boar taint. Although effective, these vaccines may cause adverse reactions at the injection site, including immunosuppression and inflammation, as well as the involvement of laborious and time-consuming procedures. Oral vaccines represent an advancement in antigen delivery technology in the vaccine industry. In this study, a serovar Typhimurium ( Typhimurium) mutant lacking the pathogenicity island 2 ( Typhimurium ΔSPI2) was used as a vehicle and mucosal adjuvant to deliver two genetic constructs in an attempt to develop an oral immunological preparation against gonadotropin hormone-releasing hormone (GnRH). Typhimurium ΔSPI2 was transformed to carry two plasmids containing a modified GnRH gene repeated in tandem (GnRXG/Q), one under eukaryotic expression control (::GnRXG/Q) and another under prokaryotic expression control (pJexpress::GnRXG/Q). A group of three male BALB/c mice were orally immunized and vaccination-boosted 30 days later. The oral administration of Typhimurium ΔSPI2 transformed with both plasmids was effective in producing antibodies against GnRXG/Q, leading to a decrease in serum testosterone levels and testicular tissue atrophy, evidenced by a reduction in the transverse tubular diameter of the seminiferous tubules and a decrease in the number of layers of the seminiferous epithelium in the testes of the inoculated mice. These results suggest that Typhimurium ΔSPI2 can be used as a safe and simple system to produce an oral formulation against GnRH and that Salmonella-mediated oral antigen delivery is a novel, yet effective, alternative to induce an immune response against GnRH in a murine model, warranting further research in other animal species.
针对促性腺激素释放激素（GnRH）的免疫接种已成功用于动物的非肠道接种，旨在控制生育能力、降低雄性攻击性并防止公猪异味。尽管这些疫苗有效，但可能会在注射部位引起不良反应，包括免疫抑制和炎症，以及涉及繁琐且耗时的程序。口服疫苗代表了疫苗行业抗原递送技术的进步。在本研究中，一种缺乏致病岛2的鼠伤寒沙门氏菌（鼠伤寒沙门氏菌ΔSPI2）突变体被用作载体和黏膜佐剂来递送两种基因构建体，试图开发一种针对促性腺激素释放激素（GnRH）的口服免疫制剂。鼠伤寒沙门氏菌ΔSPI2被转化以携带两个质粒，其中一个含有串联重复的修饰GnRH基因（GnRXG/Q），一个在真核表达控制下（::GnRXG/Q），另一个在原核表达控制下（pJexpress::GnRXG/Q）。一组三只雄性BALB/c小鼠经口服免疫，并在30天后进行加强免疫。口服同时携带两种质粒的鼠伤寒沙门氏菌ΔSPI2可有效产生针对GnRXG/Q的抗体，导致血清睾酮水平降低和睾丸组织萎缩，接种小鼠睾丸的生精小管横径减小和生精上皮层数减少证明了这一点。这些结果表明，鼠伤寒沙门氏菌ΔSPI2可作为一种安全且简单的系统来生产针对GnRH的口服制剂，并且沙门氏菌介导的口服抗原递送是在小鼠模型中诱导针对GnRH的免疫反应的一种新颖且有效的替代方法，值得在其他动物物种中进一步研究。
