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Co-administration of rlpaB domain of Shigella with rGroEL of s. Typhi enhances the immune responses and protective efficacy against Shigella infection

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Cellular & Molecular Immunology 2015年第6期12卷 757-767页

作者： Sekar Tamil Selvi Chitradevi Gurpreet Kaur Sivaramakrishna Uppalapati anandprakash yadav Dependrapratap Singh1 Anju Bansal Division of Experimental Biology Defence Institute of Physiology and Allied Sciences Delhi India Division of Microbiology Defence Food Research Laboratory Mysore India Division of Immunomodulation Defence Institute of Physiology and Allied Sciences Delhi India

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 （rlpaB） of S. flexneri, rlpaB 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. flexneriwas amplified from an invasion plasmid, cloned, expressed in BL21 Escherichia colicells and purified. Immunization with the rlpaB domain alone stimulated both humoral and cell-mediated immune responses. Furthermore, robust antibody （IgG, IgA） and T-cell responses were induced when the rlpaB domain was co-administered with rGroEL. Antibody isotyping revealed higher IgG 1 and IgG2a antibody titers and increased interferon-gamma （IFN-γ） secretion in the co-administered group. Immunization of mice with the rlpaB domain alone protected 60%-70% of the mice from lethal infection by S. flexneri, S. boydiiand 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 rlpaB domain alone. This study emphasizes that the co-administration of the rlpaB 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.

关键词： GroEL heat shock protein IpaB Shigella S. Typhi

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