title: Co-expression of S. Typhi GroEL and IL-22 gene augments immune responses against Salmonella infection.
abstract: Recombinant DNA vaccines represent a novel method for generating in situ expression of vaccine antigens. Intramuscular injections of naked DNA are able to elicit potent humoral and cellular immune responses but still numerous factors limit the immunogenicity of DNA vaccines. Co-expression of cytokines with antigen encoding genes in DNA vectors can improve the immune responses and modify Th1/Th2 balance. In this study, the immunomodulatory effect of Interleukin 22 (IL-22) as an adjuvant was studied by DNA vaccination with S. Typhi Heat shock protein 60 (HSP60/GroEL) in mice. Further, DNA construct of IL-22 gene fused with GroEL was developed and immunization studies were carried out in mice. DNA vaccination with GroEL alone stimulated humoral and cell-mediated immune responses. Co-immunization (IL-22+GroEL) further resulted in increase in T-cell proliferative responses, antibody titres (IgG, IgG1, IgG2a) and secretion of IFNγ (Th1), IL-1β and Th2 (IL-4, IL-6) cytokines. Co-expression (IL-22-GroEL DNA) also promoted antibody titres and cytokine levels were significantly higher as compared to co-immunized group. A reduction in bacterial load in spleen, liver and intestine was seen in all the immunized groups as compared to control, with least organ burden in fusion DNA construct group (co-expression). Improved protective efficacy (90%) against lethal challenge by Salmonella was observed with IL-22-GroEL co-expressing DNA vector as compared with plasmid encoding GroEL only (50-60%) or co-immunization group (75-80%). This study thus shows that co-expression of IL-22 and GroEL genes enhances the immune responses and protective efficacy, circumventing the need of any adjuvant.
authors.affiliation: Division of Experimental Biology, Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organization, Timarpur, Delhi, India.
authors.forename: Gurpreet
authors.initials: G
authors.lastname: Kaur
authors.forename: Chitradevi
authors.initials: C
authors.lastname: STS
authors.forename: Charu
authors.initials: C
authors.lastname: Nimker
authors.forename: Mrinalini
authors.initials: M
authors.lastname: Singh
authors.forename: Deepika
authors.initials: D
authors.lastname: Saraswat
authors.forename: Shweta
authors.initials: S
authors.lastname: Saxena
authors.forename: Anju
authors.initials: A
authors.lastname: Bansal
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D058491:Bacterial Load / Q000276:immunology; D049109:Cell Proliferation; D018834:Chaperonin 60 / Q000235:genetics*; D016207:Cytokines / Q000378:metabolism; D004274:DNA, Recombinant / Q000235:genetics / Q000627:therapeutic use; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors / Q000378:metabolism; D007109:Immunity / Q000235:genetics*; D007074:Immunoglobulin G / Q000276:immunology; D007378:Interleukins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis; D014176:Protein Biosynthesis; D012481:Salmonella Infections, Animal / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology* / Q000517:prevention & control; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014158:Transcription, Genetic; D016896:Treatment Outcome; D019444:Vaccines, DNA / Q000276:immunology / Q000627:therapeutic use; D000097043:Interleukin-22
chemical_list: D018834:Chaperonin 60; D016207:Cytokines; D004274:DNA, Recombinant; D007074:Immunoglobulin G; D007378:Interleukins; D009569:Nitric Oxide; D019444:Vaccines, DNA; D000097043:Interleukin-22