{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T11:57:56Z","timestamp":1753876676630,"version":"3.41.2"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T00:00:00Z","timestamp":1612224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009950","name":"Ministry of Education","doi-asserted-by":"publisher","award":["2019R1A6A1A03033084"],"award-info":[{"award-number":["2019R1A6A1A03033084"]}],"id":[{"id":"10.13039\/100009950","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,19]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>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.<\/jats:p>","DOI":"10.1093\/femspd\/ftab002","type":"journal-article","created":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T03:43:42Z","timestamp":1610509422000},"source":"Crossref","is-referenced-by-count":2,"title":["Comparative study of sodium bicarbonate- and magnesium hydroxide-based gastric antacids for the effectiveness of <i>Salmonella<\/i> delivered <i>Brucella<\/i> antigens against wild type challenge in BALB\/c mice"],"prefix":"10.1093","volume":"79","author":[{"given":"Chamith","family":"Hewawaduge","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Jeonbuk National University, Iksan Campus, 54596, Iksan, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amal","family":"Senevirathne","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Jeonbuk National University, Iksan Campus, 54596, Iksan, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myeon-Sik","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Jeonbuk National University, Iksan Campus, 54596, Iksan, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tae-Won","family":"Jeong","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Jeonbuk National University, Iksan Campus, 54596, Iksan, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bumseok","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Jeonbuk National University, Iksan Campus, 54596, Iksan, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2950-4080","authenticated-orcid":false,"given":"John Hwa","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Jeonbuk National University, Iksan Campus, 54596, Iksan, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,2,2]]},"reference":[{"key":"2021022001474841800_bib1","doi-asserted-by":"crossref","DOI":"10.1016\/0264-410X(90)90247-J","article-title":"Brucella suis S2, Brucella melitensis Rev. 1 and Brucella abortus S19 living vaccines: residual virulence and immunity induced against three Brucella species challenge strains in mice","author":"Bosseray","year":"1990","journal-title":"Vaccine"},{"key":"2021022001474841800_bib2","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0087411","article-title":"A low gastric pH mouse model to evaluate live attenuated bacterial vaccines","author":"Brenneman","year":"2014","journal-title":"PLoS One"},{"key":"2021022001474841800_bib4","doi-asserted-by":"crossref","DOI":"10.1046\/j.1365-2036.2002.01380.x","article-title":"Clinical effectiveness of a new antacid chewing gum on heartburn and oesophageal pH control","author":"Collings","year":"2002","journal-title":"Aliment Pharmacol Ther"},{"key":"2021022001474841800_bib5","article-title":"Brucellosis in humans and animals Brucellosis in humans and animals","author":"Corbel","year":"2006","journal-title":"WHO Libr Cat Publ Data"},{"key":"2021022001474841800_bib3","doi-asserted-by":"crossref","DOI":"10.1128\/CMR.5.3.328","article-title":"Oral immunization using live attenuated Salmonella spp. as carriers of foreign antigens","author":"C\u00e1rdenas","year":"1992","journal-title":"Clin Microbiol Rev"},{"key":"2021022001474841800_bib6","doi-asserted-by":"crossref","DOI":"10.18203\/2319-2003.ijbcp20195764","article-title":"Preliminary in-vitro evaluation of marketed formulations for antacid activity","author":"Dhawal","year":"2019","journal-title":"Int J Basic Clin Pharmacol"},{"key":"2021022001474841800_bib7","doi-asserted-by":"crossref","DOI":"10.1093\/infdis\/159.4.766","article-title":"Comparative efficacy of two, three, or four doses of TY21a live oral typhoid vaccine in enteric-coated capsules: a field trial in an endemic area","author":"Ferreccio","year":"1989","journal-title":"J Infect Dis"},{"key":"2021022001474841800_bib8","doi-asserted-by":"crossref","DOI":"10.1161\/01.CIR.12.4.630","article-title":"The relationship of sodium retention and venous pressures to edema formation","author":"Goldman","year":"1955","journal-title":"Circulation"},{"key":"2021022001474841800_bib10","doi-asserted-by":"crossref","DOI":"10.1128\/IAI.70.7.3457-3467.2002","article-title":"Characterization of Salmonella enterica derivatives harboring defined aroC and Salmonella pathogenicity island 2 type III secretion system (ssaV) mutations by immunization of healthy volunteers","author":"Hindle","year":"2002","journal-title":"Infect Immun"},{"key":"2021022001474841800_bib11","article-title":"Comparisons of brucellosis between human and veterinary medicine","author":"Hull","year":"2018","journal-title":"Infect Ecol Epidemiol"},{"key":"2021022001474841800_bib12","doi-asserted-by":"crossref","DOI":"10.1292\/jvms.11-0087","article-title":"Immune responses to new vaccine candidates constructed by a live attenuated Salmonella typhimurium delivery system expressing Escherichia coli F4, F5, F6, F41 and intimin adhesin antigens in a murine model","author":"Hur","year":"2011","journal-title":"J Vet Med Sci"},{"key":"2021022001474841800_bib13","doi-asserted-by":"crossref","DOI":"10.1128\/IAI.66.8.3758-3766.1998","article-title":"Interactions of the invasive pathogens Salmonellatyphimurium, Listeria monocytogenes, and Shigella flexneri with M cells and murine peyer's patches","author":"Jensen","year":"1998","journal-title":"Infect Immun"},{"key":"2021022001474841800_bib14","doi-asserted-by":"crossref","DOI":"10.1016\/S1286-4579(01)01478-2","article-title":"The role of M cells in Salmonella infection","author":"Jepson","year":"2001","journal-title":"Microbes Infect"},{"key":"2021022001474841800_bib15","doi-asserted-by":"crossref","DOI":"10.1016\/j.ajem.2008.01.030","article-title":"Paradoxical hypomagnesemia caused by excessive ingestion of magnesium hydroxide","author":"Joo\u00a0Suk","year":"2008","journal-title":"Am J Emerg Med"},{"key":"2021022001474841800_bib16","doi-asserted-by":"crossref","DOI":"10.1080\/21645515.2016.1238536","article-title":"Presentation matters: buffers, packaging, and delivery devices for new, oral enteric vaccines for infants","author":"Lal","year":"2017","journal-title":"Hum Vaccines Immunother"},{"key":"2021022001474841800_bib17","doi-asserted-by":"crossref","DOI":"10.1016\/j.vetmic.2017.05.012","article-title":"Brucella lipopolysaccharide reinforced Salmonella delivering Brucella immunogens protects mice against virulent challenge","author":"Lalsiamthara","year":"2017","journal-title":"Vet Microbiol"},{"key":"2021022001474841800_bib18","doi-asserted-by":"crossref","DOI":"10.4142\/jvs.2017.18.S1.281","article-title":"Development and trial of vaccines against Brucella","author":"Lalsiamthara","year":"2017","journal-title":"J Vet Sci"},{"key":"2021022001474841800_bib19","article-title":"Pathogenic traits of Salmonella Montevideo in experimental infections in vivo and in vitro","author":"Lalsiamthara","year":"2017","journal-title":"Sci Rep"},{"key":"2021022001474841800_bib20","doi-asserted-by":"crossref","DOI":"10.1186\/1741-7007-8-129","article-title":"Immunogenicity and efficacy of oral vaccines in developing countries: Lessons from a live cholera vaccine","author":"Levine","year":"2010","journal-title":"BMC Biol"},{"key":"2021022001474841800_bib21","doi-asserted-by":"crossref","DOI":"10.3390\/lubricants2010021","article-title":"Lubricants in pharmaceutical solid dosage forms","author":"Li","year":"2014","journal-title":"Lubricants"},{"key":"2021022001474841800_bib22","doi-asserted-by":"crossref","DOI":"10.1139\/cjm-2017-0179","article-title":"Brucella melitensis M5-90\u0394bp26 as a potential live vaccine that allows for the distinction between natural infection and immunization","author":"Li","year":"2017","journal-title":"Can J Microbiol"},{"key":"2021022001474841800_bib23","doi-asserted-by":"crossref","DOI":"10.1185\/030079908X280662","article-title":"The effect of a combination antacid preparation containing aluminium hydroxide and magnesium hydroxide on rosuvastatin pharmacokinetics","author":"Martin","year":"2008","journal-title":"Curr Med Res Opin"},{"key":"2021022001474841800_bib24","doi-asserted-by":"crossref","DOI":"10.1211\/jpp.60.1.0008","article-title":"Measurements of rat and mouse gastrointestinal pH, fluid and lymphoid tissue, and implications for in-vivo experiments","author":"McConnell","year":"2008","journal-title":"J Pharm Pharmacol"},{"key":"2021022001474841800_bib25","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1128\/IAI.72.4.2081-2087.2004","article-title":"Intraspleen delivery of a DNA vaccine coding for Superoxide Dismutase (SOD) of Brucella abortus induces SOD-Specific CD4+ and CD8+ T cells","volume":"72","author":"Mu\u00f1oz-Montesino","year":"2004","journal-title":"Infect Immun"},{"key":"2021022001474841800_bib26","doi-asserted-by":"crossref","DOI":"10.1155\/2019\/4518163","article-title":"Evaluation of different stabilizers and inactivating compounds for the enhancement of vero cell rabies vaccine stability and immunogenicity: in vitro study","author":"Olayan","year":"2019","journal-title":"Biomed Res Int"},{"key":"2021022001474841800_bib27","doi-asserted-by":"crossref","DOI":"10.1111\/j.1365-2958.1993.tb01198.x","article-title":"Influence of pH on bacterial gene expression","author":"Olson","year":"1993","journal-title":"Mol Microbiol"},{"key":"2021022001474841800_bib28","doi-asserted-by":"crossref","DOI":"10.1111\/j.1600-065X.2010.00970.x","article-title":"Immunology of gut mucosal vaccines","author":"Pasetti","year":"2011","journal-title":"Immunol Rev"},{"key":"2021022001474841800_bib29","doi-asserted-by":"crossref","DOI":"10.1128\/IAI.00123-09","article-title":"Immunization with recombinant Brucella species outer membrane protein Omp16 or Omp19 in adjuvant induces specific CD4+ and CD8+ T cells as well as systemic and oral protection against Brucella abortus infection","author":"Pasquevich","year":"2009","journal-title":"Infect Immun"},{"key":"2021022001474841800_bib30","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms13520","article-title":"Additives for vaccine storage to improve thermal stability of adenoviruses from hours to months","author":"Pelliccia","year":"2016","journal-title":"Nat Commun"},{"key":"2021022001474841800_bib31","doi-asserted-by":"crossref","DOI":"10.1128\/JB.00105-13","article-title":"The Escherichia coli Cpx envelope stress response regulates genes of diverse function that impact antibiotic resistance and membrane integrity","author":"Raivio","year":"2013","journal-title":"J Bacteriol"},{"key":"2021022001474841800_bib32","doi-asserted-by":"crossref","DOI":"10.1046\/j.1365-2036.2002.01178.x","article-title":"Effects of antacid formulation on postprandial oesophageal acidity in patients with a history of episodic heartburn","author":"Robinson","year":"2002","journal-title":"Aliment Pharmacol Ther"},{"key":"2021022001474841800_bib33","doi-asserted-by":"crossref","DOI":"10.1128\/IAI.65.6.2107-2111.1997","article-title":"Comparison of alternative buffers for use with a new live oral cholera vaccine, Peru-15, in outpatient volunteers","author":"Sack","year":"1997","journal-title":"Infect Immun"},{"key":"2021022001474841800_bib34","article-title":"Salmonellae as oral vaccine carriers","volume":"84","author":"Sch\u00f6del","year":"1995","journal-title":"Dev Biol Stand"},{"key":"2021022001474841800_bib35","doi-asserted-by":"crossref","DOI":"10.1016\/j.vetimm.2019.02.001","article-title":"Attenuated Salmonella secreting Brucella protective antigens confer dual-faceted protection against brucellosis and salmonellosis in a mouse model","author":"Senevirathne","year":"2019","journal-title":"Vet Immunol Immunopathol"},{"key":"2021022001474841800_bib37","doi-asserted-by":"crossref","DOI":"10.1007\/s00540-008-0612-8","article-title":"Critical alkalosis following intraperitoneal irrigation with sodium bicarbonate in a patient with Pseudomyxoma peritonei","author":"Shirasawa","year":"2008","journal-title":"J Anesth"},{"key":"2021022001474841800_bib36","doi-asserted-by":"crossref","DOI":"10.1016\/j.virol.2014.07.011","article-title":"Immunoprotection against influenza virus H9N2 by the oral administration of recombinant Lactobacillus plantarumNC8 expressing hemagglutinin in BALB\/c mice","author":"Shi","year":"2014","journal-title":"Virology"},{"key":"2021022001474841800_bib38","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1128\/IAI.65.2.452-456.1997","article-title":"Safety of live oral Salmonella typhi vaccine strains with deletions in htrA and aroC aroD and immune response in humans","volume":"65","author":"Tacket","year":"1997","journal-title":"Infect Immun"},{"key":"2021022001474841800_bib39","doi-asserted-by":"crossref","DOI":"10.1128\/IAI.71.2.690-696.2003","article-title":"Lon, a stress-induced ATP-dependent protease, is critically important for systemic Salmonellaenterica serovar typhimurium infection of mice","author":"Takaya","year":"2003","journal-title":"Infect Immun"},{"key":"2021022001474841800_bib40","article-title":"Calcium signaling in immune cells","author":"Vig","year":"2009","journal-title":"Nat Immunol"},{"key":"2021022001474841800_bib41","doi-asserted-by":"crossref","DOI":"10.3748\/wjg.v16.i35.4455","article-title":"Antacid effects of Chinese herbal prescriptions assessed by a modified artificial stomach model","author":"Wu","year":"2010","journal-title":"World J Gastroenterol"},{"key":"2021022001474841800_bib42","doi-asserted-by":"crossref","DOI":"10.1186\/s12917-015-0497-3","article-title":"Immunogenicity and protective efficacy of Salmonella enterica serovar Pullorum pathogenicity island 2 mutant as a live attenuated vaccine candidate","author":"Yin","year":"2015","journal-title":"BMC Vet Res"},{"key":"2021022001474841800_bib43","doi-asserted-by":"crossref","DOI":"10.4161\/gmic.24197","article-title":"Oral vaccines: directed safe passage to the front line of defense","author":"Zhu","year":"2013","journal-title":"Gut Microbes"}],"container-title":["Pathogens and Disease"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/femspd\/advance-article-pdf\/doi\/10.1093\/femspd\/ftab002\/36171492\/ftab002.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/femspd\/article-pdf\/79\/2\/ftab002\/36325718\/ftab002.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/femspd\/article-pdf\/79\/2\/ftab002\/36325718\/ftab002.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,21]],"date-time":"2021-02-21T06:15:14Z","timestamp":1613888114000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/femspd\/article\/doi\/10.1093\/femspd\/ftab002\/6126344"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,2]]},"references-count":42,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,2,19]]}},"URL":"https:\/\/doi.org\/10.1093\/femspd\/ftab002","relation":{},"ISSN":["2049-632X"],"issn-type":[{"type":"electronic","value":"2049-632X"}],"subject":[],"published-other":{"date-parts":[[2021,3]]},"published":{"date-parts":[[2021,2,2]]},"article-number":"ftab002"}}