PMID- 31705999 OWN - NLM STAT- MEDLINE DCOM- 20200605 LR - 20200605 IS - 1096-1208 (Electronic) IS - 0882-4010 (Linking) VI - 138 DP - 2020 Jan TI - Enhancement of host infectivity, immunity, and protective efficacy by addition of sodium bicarbonate antacid to oral vaccine formulation of live attenuated Salmonella secreting Brucella antigens. PG - 103857 LID - S0882-4010(19)31530-X [pii] LID - 10.1016/j.micpath.2019.103857 [doi] AB - In the present study, the importance of sodium bicarbonate antacid as an agent for an orally delivered attenuated Salmonella strain secreting Brucella antigens Cu-Zn superoxide dismutase (SodC) and outer membrane protein 19 (Omp19) as a live vaccine candidate against Brucella infection was investigated. First, Brucella antigens SodC and Omp19 were cloned into a prokaryotic constitutive expression vector, pJHL65. Then secretion of proteins was verified after transformation into an attenuated Salmonella typhimurium (ST) strain, JOL1800 (Deltalon, DeltacpxR, Deltaasd, DeltarfaL), using western blot analysis. Mice were orally inoculated with phosphate-buffered saline (PBS) or with a co-mixture Salmonella secreting each antigens at a 1:1 ratio, each containing 1 x 10(8) CFU/mouse with and without sodium bicarbonate treatment. For antacid treatment, 1.3% w/v sodium bicarbonate was orally administered 30 min before and immediately after immunization with the Salmonella formulation. Humoral and cell-mediated immune responses were evaluated to investigate the efficacy of sodium bicarbonate in an oral formulation. The results indicated that addition of sodium bicarbonate to the vaccine significantly increased (P < 0.05) levels of anti-Brucella-specific systemic IgG responses, lymphocyte proliferation, and CD4(+) T cell responses, indicating induction of a mixed Th1-Th2 response. Immunohistochemical assays and bacterial enumeration in intestinal samples also indicated that administration of sodium bicarbonate enhanced colonization of Salmonella. These results indicate that ingestion of the Salmonella formulation with sodium bicarbonate can enhance colonization of Salmonella and induce a significant protective immune response against Brucella compared with a formulation without sodium bicarbonate. Thus, incorporation of sodium bicarbonate as an antacid buffer is highly recommended for this oral live vaccine. CI - Copyright (c) 2019 Elsevier Ltd. All rights reserved. FAU - Hewawaduge, Chamith AU - Hewawaduge C AD - College of Veterinary Medicine, Jeonbuk National University, Iksan Campus, 54596, Iksan, Republic of Korea. FAU - Senevirathne, Amal AU - Senevirathne A AD - College of Veterinary Medicine, Jeonbuk National University, Iksan Campus, 54596, Iksan, Republic of Korea. FAU - Lee, John Hwa AU - Lee JH AD - College of Veterinary Medicine, Jeonbuk National University, Iksan Campus, 54596, Iksan, Republic of Korea. Electronic address: johnhlee@jbnu.ac.kr. LA - eng PT - Journal Article DEP - 20191106 PL - England TA - Microb Pathog JT - Microbial pathogenesis JID - 8606191 RN - 0 (Antigens, Bacterial) RN - 0 (Bacterial Vaccines) RN - 0 (Brucella Vaccine) RN - 0 (Vaccines, Attenuated) RN - 8MDF5V39QO (Sodium Bicarbonate) SB - IM MH - Administration, Oral MH - Animals MH - Antigens, Bacterial/immunology MH - Bacterial Vaccines/administration & dosage/biosynthesis/chemistry MH - *Brucella Vaccine/administration & dosage/biosynthesis/chemistry MH - Immunity, Cellular MH - Immunity, Humoral MH - Intestines/immunology/microbiology MH - Mice MH - Microorganisms, Genetically-Modified MH - Salmonella typhimurium/genetics/immunology MH - *Sodium Bicarbonate/administration & dosage MH - Transformation, Bacterial MH - Vaccination/methods MH - *Vaccines, Attenuated/administration & dosage/biosynthesis/chemistry OTO - NOTNLM OT - Antacid agent OT - Brucella OT - Humoral and cell-mediated immunity OT - Oral vaccination OT - Salmonella typhimurium COIS- Declaration of competing interest The authors declare that they have no competing interests. EDAT- 2019/11/11 06:00 MHDA- 2020/06/06 06:00 CRDT- 2019/11/10 06:00 PHST- 2019/08/28 00:00 [received] PHST- 2019/11/05 00:00 [revised] PHST- 2019/11/05 00:00 [accepted] PHST- 2019/11/11 06:00 [pubmed] PHST- 2020/06/06 06:00 [medline] PHST- 2019/11/10 06:00 [entrez] AID - S0882-4010(19)31530-X [pii] AID - 10.1016/j.micpath.2019.103857 [doi] PST - ppublish SO - Microb Pathog. 2020 Jan;138:103857. doi: 10.1016/j.micpath.2019.103857. Epub 2019 Nov 6.