A recombinant protein of Salmonella Typhi induces humoral and cell-mediated immune responses including memory responses. Issue 35 (16th August 2017)

• Record Type: Journal Article
• Authors: Das, Sayan; Chowdhury, Rimi; Ghosh, Shubhamoy; Das, Santasabuj
• Is Part Of: Vaccine. Volume 35:Issue 35(2017)Part B
• Page Start: 4523
• Page End: 4531
• Publication Date: 2017-08-16
• Subjects: CFU colony forming units -- MLN mesenteric lymph node -- PP peyer's patch -- LDH lactate dehydrogenase -- CFSE carboxyfluorescein succinimidyl ester -- OMP outer membrane protein -- EPA pseudomonas aeruginosa exoprotein A; Salmonella enteric serovar Typhi -- Typhoid -- Vaccine -- rT2544 -- Immunological memory -- Vi polysaccharide; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2017.07.035
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: Existing vaccines against typhoid fever, a global public health problem are modestly efficacious. Candidate protein subunit vaccine induced IgG and IgA secreting plasma cells and memory B cells. IFN-γ-producing cytotoxic T lymphocytes with antigen-specific cytotoxicity were also generated. Candidate vaccine induced T cell proliferation, Th1 cytokine release and memory T cell response. Abstract: 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.