Hewawaduge Chamith, Senevirathne Amal, Yang Myeon-Sik, Jeong Tae-Won, Kim Bumseok, Lee John Hwa
College of Veterinary Medicine, Jeonbuk National University, Iksan Campus, 54596, Iksan, Republic of Korea.
Pathog Dis. 2021 Feb 19;79(2). doi: 10.1093/femspd/ftab002.
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.
我们比较了两种基于碳酸氢钠和氢氧化镁的抗酸剂配方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pH缓冲能力、缓冲持久性以及这些配方在中和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强、更稳定和更持久的缓冲能力,口服时更安全。口服碳酸氢钠会导致小鼠行为反映出的不适和轻微肌肉震颤,而用氢氧化镁和磷酸盐缓冲盐水处理的小鼠完全正常。使用BALB/c小鼠进行的胃内存活研究表明,当给予基于氢氧化镁的抗酸缓冲剂时,更多的沙门氏菌到达肠道。将分泌布鲁氏菌抗原、超氧化物歧化酶C(SodC)和外膜蛋白19(Omp19)的减毒沙门氏菌与单独的抗酸剂配方共同给药,可显著增强针对强毒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,预先接种疫苗口服碳酸氢钠-柠檬酸或氢氧化镁基中和缓冲剂可通过维持口服肠道疫苗制剂的活力来显著抵消胃酸。