Use of Ensure® nutrition shakes as an alternative formulation method for live recombinant Attenuated Salmonella Typhi vaccines

BMC Microbiology

Roy Curtiss¹  Kenneth L Roland³  Amanda Gonzales³  Karen E Brenneman² 

[1] School of Life Sciences, Arizona State University, Tempe 85287, AZ, USA;Present address - 23andMe, Inc, 1390 Shorebird Way, Mountain View 94043, CA, USA;The Biodesign Institute, Arizona State University, Tempe 85287, AZ, USA

关键词: Low gastric pH mouse model;    Ensure nutrition shake;    Bicarbonate;    Gastric pH neutralization;    Salmonella vaccine;   

Others  :  1212075
DOI  :  10.1186/s12866-015-0409-5

 received in 2014-12-01, accepted in 2015-03-12,  发布年份 2015

【 摘 要 】

Background

To be effective, orally administered live Salmonella vaccines must first survive their encounter with the low pH environment of the stomach. To enhance survival, an antacid is often given to neutralize the acidic environment of the stomach just prior to or concomitant with administration of the vaccine. One drawback of this approach, from the perspective of the clinical trial volunteer, is that the taste of a bicarbonate-based acid neutralization system can be unpleasant. Thus, we explored an alternative method that would be at least as effective as bicarbonate and with a potentially more acceptable taste. Because ingestion of protein can rapidly buffer stomach pH, we examined the possibility that the protein-rich Ensure® Nutrition shakes would be effective alternatives to bicarbonate.

Results

We tested one Salmonella enterica serovar Typhimurium and three Salmonella Typhi vaccine strains and found that all strains survived equally well when incubated in either Ensure® or bicarbonate. In a low gastric pH mouse model, Ensure® worked as well or better than bicarbonate to enhance survival through the intestinal tract, although neither agent enhanced the survival of the S. Typhi test strain possessing a rpoS mutation.

Conclusions

Our data show that a protein-rich drink such as Ensure® Nutrition shakes can serve as an alternative to bicarbonate for reducing gastric pH prior to administration of a live Salmonella vaccine.

【 授权许可】

   
2015 Brenneman et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Curtiss R, Xin W, Li Y, Kong W, Wanda SY, Gunn B et al.. New technologies in using recombinant attenuated Salmonella vaccine vectors. Crit Rev Immunol. 2010; 30:255-70.
• [2]Curtiss R, Zhang X, Wanda S-Y, Kang HY, Konjufca V, Gunn B et al.. Induction of host immune responses using Salmonella-vectored vaccines. Virulence mechanisms of bacterial pathogens. 4th ed. Brodgen K, Minion F, Cornick N, Stanton T, Zhange Q, Nolan L, Wannemuehler M, editors. ASM Press, Washington, DC; 2007.
• [3]Cardenas L, Clements JD. Oral immunization using live attenuated Salmonella spp. as carriers of foreign antigens. Clin Microbiol Rev. 1992; 5:328-42.
• [4]Verdu E, Viani F, Armstrong D, Fraser R, Siegrist HH, Pignatelli B et al.. Effect of omeprazole on intragastric bacterial counts, nitrates, nitrites, and N-nitroso compounds. Gut. 1994; 35:455-60.
• [5]Kararli TT. Comparison of the gastrointestinal anatomy, physiology, and biochemistry of humans and commonly used laboratory animals. Biopharm Drug Dispos. 1995; 16:351-80.
• [6]Hone DM, Harris AM, Levine MM. Adaptive acid tolerance response by Salmonella typhi and candidate live oral typhoid vaccine strains. Vaccine. 1994; 12:895-8.
• [7]Lee IS, Lin J, Hall HK, Bearson B, Foster JW. The stationary-phase sigma factor sigma S (RpoS) is required for a sustained acid tolerance response in virulent Salmonella typhimurium. Mol Microbiol. 1995; 17:155-67.
• [8]Lin J, Lee IS, Frey J, Slonczewski JL, Foster JW. Comparative analysis of extreme acid survival in Salmonella typhimurium, Shigella flexneri, and Escherichia coli. J Bacteriol. 1995; 177:4097-104.
• [9]Bearson BL, Wilson L, Foster JW. A low pH-inducible, PhoPQ-dependent acid tolerance response protects Salmonella Typhimurium against inorganic acid stress. J Bacteriol. 1998; 180:2409-17.
• [10]Hall HK, Foster JW. The role of fur in the acid tolerance response of Salmonella Typhimurium is physiologically and genetically separable from its role in iron acquisition. J Bacteriol. 1996; 178:5683-91.
• [11]Robbe-Saule V, Coynault C, Norel F. The live oral typhoid vaccine Ty21a is a rpoS mutant and is susceptible to various environmental stresses. FEMS Microbiol Lett. 1995; 126:171-6.
• [12]Curtiss R, Wanda SY, Gunn BM, Zhang X, Tinge SA, Ananthnarayan V et al.. Salmonella enterica serovar Typhimurium strains with regulated delayed attenuation in vivo. Infect Immun. 2009; 77:1071-82.
• [13]Shi H, Santander J, Brenneman KE, Wanda SY, Wang S, Senechal P et al.. Live recombinant Salmonella Typhi vaccines constructed to investigate the role of rpoS in eliciting immunity to a heterologous antigen. PLoS One. 2010; 5:e11142.
• [14]Tacket CO, Sztein MB, Losonsky GA, Wasserman SS, Nataro JP, Edelman R et al.. Safety of live oral Salmonella typhi vaccine strains with deletions in htrA and aroC aroD and immune response in humans. Infect Immun. 1997; 65:452-6.
• [15]Hindle Z, Chatfield SN, Phillimore J, Bentley M, Johnson J, Cosgrove CA et al.. Characterization of Salmonella enterica derivatives harboring defined aroC and Salmonella pathogenicity island 2 type III secretion system (ssaV) mutations by immunization of healthy volunteers. Infect Immun. 2002; 70:3457-67.
• [16]Gilman RH, Hornick RB, Woodard WE, DuPont HL, Snyder MJ, Levine MM et al.. Evaluation of a UDP-glucose-4-epimeraseless mutant of Salmonella typhi as a live oral vaccine. J Infect Dis. 1977; 136:717-23.
• [17]Frey SE, Bollen W, Sizemore D, Campbell M, Curtiss R. Bacteremia associated with live attenuated χ8110 Salmonella enterica serovar Typhi ISP1820 in healthy adult volunteers. Clin Immunol. 2001; 101:32-7.
• [18]Simmons TC, Hogan DL, Selling JA, Maxwell V, Isenberg JI. The effect of sodium bicarbonate versus aluminum-magnesium hydroxide on postprandial gastric acid in duodenal ulcer patients. J Clin Gastroenterol. 1986; 8:146-9.
• [19]Kajikawa A, Nordone SK, Zhang L, Stoeker LL, LaVoy AS, Klaenhammer TR et al.. Dissimilar properties of two recombinant Lactobacillus acidophilus strains displaying Salmonella FliC with different anchoring motifs. Appl Environ Microbiol. 2011; 77:6587-96.
• [20]Black RE, Levine MM, Ferreccio C, Clements ML, Lanata C, Rooney J et al.. Efficacy of one or two doses of Ty21a Salmonella typhi vaccine in enteric-coated capsules in a controlled field trial. Vaccine. 1990; 8:81-4.
• [21]Levine MM, Ferreccio C, Abrego P, Martin OS, Ortiz E, Cryz S. Duration of efficacy of Ty21a, attenuated Salmonella typhi live oral vaccine. Vaccine. 1999; 17 Suppl 2:S22-7.
• [22]Holdsworth JD, Johnson K, Mascall G, Roulston RG, Tomlinson PA. Mixing of antacids with stomach contents. Another approach to the prevention of the acid aspiration (Mendelson’s) syndrome. Anaesthesia. 1980; 35:641-50.
• [23]Chen CT, Toung TJ, Haupt HM, Hutchins GM, Cameron JL. Evaluation of the efficacy of Alka-Seltzer Effervescent in gastric acid neutralization. Anesth Analg. 1984; 63:325-9.
• [24]Ahmed T, Bhuiyan TR, Zaman K, Sinclair D, Qadri F. Vaccines for preventing enterotoxigenic Escherichia coli (ETEC) diarrhoea. Cochrane Database Syst Rev. 2013; 7:CD009029.
• [25]Saint-Hilaire S, Lavers MK, Kennedy J, Code CF. Gastric acid secretory value of different foods. Gastroenterology. 1960; 39:1-11.
• [26]Maner J, Pond W, Loosli J, Lowrey R. Effect of isolated soybean protein and casein on the gastric pH and rate of passage of food residues in baby pigs. J Anim Sci. 1962; 21:49-52.
• [27]Waterman SR, Small PL. Acid-sensitive enteric pathogens are protected from killing under extremely acidic conditions of pH 2.5 when they are inoculated onto certain solid food sources. Appl Environ Microbiol. 1998; 64:3882-6.
• [28]McConnell EL, Basit AW, Murdan S. Measurements of rat and mouse gastrointestinal pH, fluid and lymphoid tissue, and implications for in-vivo experiments. J Pharm Pharmacol. 2008; 60:63-70.
• [29]Brenneman KE, Willingham C, Kilbourne JA, Curtiss R, Roland KL. A low gastric pH mouse model to evaluate live attenuated bacterial vaccines. PLoS One. 2014; 9:e87411.
• [30]Black R, Levine MM, Young C, Rooney J, Levine S, Clements ML et al.. Immunogenicity of Ty21a attenuated Salmonella typhi given with sodium bicarbonate or in enteric-coated capsules. Dev Biol Stand. 1983; 53:9-14.
• [31]Wahdan MH, Serie C, Germanier R, Lackany A, Cerisier Y, Guerin N et al.. A controlled field trial of live oral typhoid vaccine Ty21a. Bull World Health Organ. 1980; 58:469-74.
• [32]Frey SE, Lottenbach KR, Hill H, Blevins TP, Yu Y, Zhang Y et al.. A Phase I, dose-escalation trial in adults of three recombinant attenuated Salmonella Typhi vaccine vectors producing Streptococcus pneumoniae surface protein antigen PspA. Vaccine. 2013; 31:4874-80.
• [33]Yang J, Dogovski C, Hocking D, Tauschek M, Perugini M, Robins-Browne RM. Bicarbonate-mediated stimulation of RegA, the global virulence regulator from Citrobacter rodentium. J Mol Biol. 2009; 394:591-9.
• [34]Robbe-Saule V, Norel F. The rpoS mutant allele of Salmonella typhi Ty2 is identical to that of the live typhoid vaccine Ty21a. FEMS Microbiol Lett. 1999; 170:141-3.
• [35]Foster JW. The acid tolerance response of Salmonella Typhimurium involves transient synthesis of key acid shock proteins. J Bacteriol. 1993; 175:1981-7.
• [36]Bertani G. Studies on lysogenesis. I. The mode of phage liberation by lysogenic Escherichia coli. J Bacteriol. 1951; 62:293-300.
• [37]Chew CS, Chen X, Bollag RJ, Isales C, Ding KH, Zhang H. Targeted disruption of the Lasp-1 gene is linked to increases in histamine-stimulated gastric HCl secretion. Am J Physiol Gastrointest Liver Physiol. 2008; 295:G37-44.
• [38]Furutani K, Aihara T, Nakamura E, Tanaka S, Ichikawa A, Ohtsu H et al.. Crucial role of histamine for regulation of gastric acid secretion ascertained by histidine decarboxylase-knockout mice. J Pharmacol Exp Ther. 2003; 307:331-8.
• [39]Li Y, Wang S, Scarpellini G, Gunn B, Xin W, Wanda SY et al.. Evaluation of new generation Salmonella enterica serovar Typhimurium vaccines with regulated delayed attenuation to induce immune responses against PspA. Proc Natl Acad Sci U S A. 2009; 106:593-8.
• [40]Curtiss R, Hassan JO. Nonrecombinant and recombinant avirulent Salmonella vaccines for poultry. Vet Immunol Immunopathol. 1996; 54:365-72.
• [41]Hone DM, Harris AM, Chatfield S, Dougan G, Levine MM. Construction of genetically defined double aro mutants of Salmonella typhi. Vaccine. 1991; 9:810-6.
• [42]Felix A, Pitt RM. The pathogenic and immunogenic activities of Salmonella typhi in relation to its antigenic constituents. J Hyg (Lond). 1951; 49:92-110.
• [43]Santander J, Wanda SY, Nickerson CA, Curtiss R. Role of RpoS in fine-tuning the synthesis of Vi capsular polysaccharide in Salmonella enterica serotype Typhi. Infect Immun. 2007; 75:1382-92.
• [44]Wang RF, Kushner SR. Construction of versatile low-copy-number vectors for cloning, sequencing and gene expression in Escherichia coli. Gene. 1991; 100:195-9.
• [45]Kang HY, Srinivasan J, Curtiss R. Immune responses to recombinant pneumococcal PspA antigen delivered by live attenuated Salmonella enterica serovar Typhimurium vaccine. Infect Immun. 2002; 70:1739-49.
• [46]Xin W, Wanda SY, Li Y, Wang S, Mo H, Curtiss R. Analysis of type II secretion of recombinant pneumococcal PspA and PspC in a Salmonella enterica serovar Typhimurium vaccine with regulated delayed antigen synthesis. Infect Immun. 2008; 76:3241-54.