title: Co-administration of rIpaB domain of Shigella with rGroEL of S. Typhi enhances the immune responses and protective efficacy against Shigella infection.
abstract: Shigella species cause severe bacillary dysentery in humans and are associated with high morbidity and mortality. The Invasion plasmid antigen (IpaB) protein, which is conserved across all Shigella spp., induces macrophage cell death and is required to invade host cells. The present study evaluates the immunogenicity and protective efficacy of the recombinant (r) domain region of IpaB (rIpaB) of S. flexneri. rIpaB was administered either alone or was co-administered with the rGroEL (heat shock protein 60) protein from S. Typhi as an adjuvant in a mouse model of intranasal immunization. The IpaB domain region (37 kDa) of S. flexneri was amplified from an invasion plasmid, cloned, expressed in BL21 Escherichia coli cells and purified. Immunization with the rIpaB domain alone stimulated both humoral and cell-mediated immune responses. Furthermore, robust antibody (IgG, IgA) and T-cell responses were induced when the rIpaB domain was co-administered with rGroEL. Antibody isotyping revealed higher IgG1 and IgG2a antibody titers and increased interferon-gamma (IFN-γ) secretion in the co-administered group. Immunization of mice with the rIpaB domain alone protected 60%-70% of the mice from lethal infection by S. flexneri, S. boydii and S. sonnei, whereas co-administration with rGroEL increased the protective efficacy to 80%-85%. Organ burden and histopathological studies also revealed a significant reduction in lung infection in the co-immunized mice compared with mice immunized with the rIpaB domain alone. This study emphasizes that the co-administration of the rIpaB domain and rGroEL protein improves immune responses in mice and increases protective efficacy against Shigella infection. This is also the first report to evaluate the potential of the GroEL (Hsp 60) protein of S. Typhi as an adjuvant molecule, thereby overcoming the need for commercial adjuvants.
authors: Division of Experimental Biology, Defence Institute of Physiology and Allied Sciences, Delhi, India.
authors: Sekar Tamil Selvi
authors: ST
authors: Chitradevi
authors: Division of Experimental Biology, Defence Institute of Physiology and Allied Sciences, Delhi, India.
authors: Gurpreet
authors: G
authors: Kaur
authors: Division of Microbiology, Defence Food Research Laboratory, Mysore, India.
authors: Sivaramakrishna
authors: S
authors: Uppalapati
authors: Division of Immunomodulation, Defence Institute of Physiology and Allied Sciences, Delhi, India.
authors: Anandprakash
authors: A
authors: Yadav
authors: Division of Experimental Biology, Defence Institute of Physiology and Allied Sciences, Delhi, India.
authors: Dependrapratap
authors: D
authors: Singh
authors: Division of Experimental Biology, Defence Institute of Physiology and Allied Sciences, Delhi, India.
authors: Anju
authors: A
authors: Bansal
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D018834:Chaperonin 60 / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D003001:Cloning, Molecular; D004405:Dysentery, Bacillary / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D007113:Immunity, Innate / Q000187:drug effects*; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D012485:Salmonella typhi / Q000737:chemistry / Q000276:immunology; D012760:Shigella / Q000187:drug effects / Q000276:immunology* / Q000472:pathogenicity; D016019:Survival Analysis
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D018834:Chaperonin 60; D011994:Recombinant Proteins; C087447:ipaB protein, Shigella; D007371:Interferon-gamma
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