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A recombinant protein of Salmonella Typhi induces humoral and cell-mediated immune responses including memory responses

Das, Sayan, Chowdhury, Rimi, Ghosh, Shubhamoy, Das, Santasabuj
Vaccine 2017 v.35 no.35 pp. 4523-4531
CD4-positive T-lymphocytes, Salmonella Typhi, antigens, antiserum, cell differentiation, cell proliferation, cell-mediated immunity, cytotoxic T-lymphocytes, cytotoxicity, dendritic cells, developing countries, etiological agents, hygiene, immunoglobulin A, immunoglobulin G, immunologic memory, interferon-gamma, interleukin-2, interleukin-6, intestinal microorganisms, lymph nodes, mice, multiple drug resistance, outer membrane proteins, plasma cells, population growth, public health, recombinant proteins, sanitation, spleen, splenocytes, tumor necrosis factor-alpha, typhoid fever, vaccination, vaccines
Gram negative enteric bacteria, Salmonella enterica serovar Typhi (S. Typhi), the etiological agent of typhoid fever is a major public health problem in developing countries. While a permanent solution to the problem would require improved sanitation, food and water hygiene, controlling the infection by vaccination is urgently required due to the emergence of multidrug resistant strains in multiple countries. The currently licensed vaccines are moderately efficacious with limited applicability, and no recommended vaccines exist for younger children.We had previously reported that a candidate vaccine based on recombinant outer membrane protein (rT2544) of S. Typhi is highly immunogenic and protective in mice. Here we show that rT2544-specific antiserum is capable of mediating bacterial lysis by the splenocytes through Antibody-Dependent Cellular Cytotoxicity (ADCC). Increased populations of rT2544-specific IgA and IgG secreting plasma cells are found in the spleen, mesenteric lymph nodes and peyer’s patches. Cell-Mediated Immune Responses (CMIR) induced by rT2544 consist of Th1 cell differentiation and generation of cytotoxic T lymphocytes (CTL), which produce IFN-γ and are capable of destroying cells displaying T2544-derived antigens. rT2544 elicits pro-inflammatory cytokines (TNF-α, IL-6) from Bone Marrow-Derived Dendritic cells (BMDCs), while in vitro re-stimulation of rT2544-primed CD4+ T cells induces cell proliferation and generates higher amounts of Th1 cytokines, such as IFN-gamma, TNF-α and IL-2. Finally, the candidate vaccine induces immunological memory in the form of memory B and T lymphocytes. Taken together, the study further supports the potential of rT2544 as a novel and improved vaccine candidate against S. Typhi.