We compared the effects of two antacid formulations based on sodium bicarbonate and magnesium hydroxide on a Salmonella-delivered oral Brucella live attenuated vaccine. We conducted a series of in vitro and in vivo experiments to investigate the pH buffering capacity, buffering longevity and the effects of these formulations on the survival of Salmonella under neutralized pH conditions and its impact on immune responses. Magnesium hydroxide had a greater, stable and prolonged buffering capacity than sodium bicarbonate and was safer when administered orally. Oral administration of sodium bicarbonate resulted in discomfort as reflected by mouse behavior and mild muscle tremors, whereas mice treated with magnesium hydroxide and PBS were completely normal. Gastric survival studies using BALB/c mice revealed that a higher number of Salmonella reached the intestine when the magnesium hydroxide-based antacid buffer was administrated. Co-administration with attenuated Salmonella secreting Brucella antigens, SodC and Omp19 along with individual antacid formulations, significantly enhanced the antigen-specific protective immune responses against virulent Brucella challenge. Together, our results indicated that the pre vaccinated oral administration of bicarbonate-citric acid or magnesium hydroxide-based neutralizing buffers significantly counteract stomach acidity by maintaining the viability of an oral enteric vaccine formulation.

中文翻译：

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基于碳酸氢钠和氢氧化镁的胃酸抗酸剂对沙门氏菌递送布鲁氏菌抗原对 BALB/c 小鼠野生型攻击的有效性的比较研究

我们比较了基于碳酸氢钠和氢氧化镁的两种抗酸剂制剂对沙门氏菌递送的口服布鲁氏菌减毒活疫苗的影响。我们进行了一系列体外和体内实验，以研究这些制剂的 pH 缓冲能力、缓冲寿命以及这些制剂在中和 pH 条件下对沙门氏菌存活的影响及其对免疫反应的影响。氢氧化镁比碳酸氢钠具有更大、稳定和延长的缓冲能力，并且在口服时更安全。口服碳酸氢钠导致不适，表现为小鼠行为和轻度肌肉震颤，而用氢氧化镁和 PBS 治疗的小鼠则完全正常。使用 BALB/c 小鼠的胃存活研究表明，当给予基于氢氧化镁的抗酸缓冲液时，更多数量的沙门氏菌到达肠道。与分泌布鲁氏菌抗原的减毒沙门氏菌、SodC 和 Omp19 以及单独的抗酸剂制剂共同给药，显着增强了针对毒力布鲁氏菌攻击的抗原特异性保护性免疫反应。总之，我们的结果表明，接种前口服碳酸氢盐-柠檬酸或氢氧化镁基中和缓冲液可通过维持口服肠道疫苗制剂的活力来显着抵消胃酸。SodC 和 Omp19 以及单独的抗酸剂配方显着增强了针对毒力布鲁氏菌攻击的抗原特异性保护性免疫反应。总之，我们的结果表明，接种前口服碳酸氢盐-柠檬酸或氢氧化镁基中和缓冲液可通过维持口服肠道疫苗制剂的活力来显着抵消胃酸。SodC 和 Omp19 以及单独的抗酸剂配方显着增强了针对毒力布鲁氏菌攻击的抗原特异性保护性免疫反应。总之，我们的结果表明，接种前口服碳酸氢盐-柠檬酸或氢氧化镁基中和缓冲液可通过维持口服肠道疫苗制剂的活力来显着抵消胃酸。