Construction of a novel tetravalent dengue vaccine with a Salmonella Typhimurium bacterial ghost and evaluation of its immunogenicity and protective efficacy using a murine model.
Vaccine
; 38(4): 916-924, 2020 01 22.
Article
em En
| MEDLINE
| ID: mdl-31706812
ABSTRACT
Efforts to develop a safe, effective, and affordable dengue vaccine have focused on providing simultaneous immunity against all four serotypes of the dengue virus (DENV). In the current study, Salmonella Typhimurium (ST) lysed by gene E activation was genetically constructed to deliver the envelope protein domain III (EDIII) of all four serotypes of DENV using a foreign antigen delivery and expression vector, pJHL184. Each DENV-EDIII protein expressed in the constructed strain was validated by immunoblot analysis. To assess the immunogenicity and protective efficacy of the constructs against dengue infection, BALB/c mice were injected once orally with either the individual ST-EDIII constructs or a mix of all four ST-EDIII constructs followed by intramuscular administration of the purified EDIII protein. Significantly elevated titers of EDIII-specific IgG, IgG1, and IgG2a were observed in the immunized mice (Pâ¯<â¯0.01). Furthermore, lymphocyte proliferative activity and CD3+CD4+ T-cell subpopulations increased significantly in vitro in re-pulsed splenic T cells compared with those from non-immunized mice. In addition, a lower viral load was detected in the BG-EDIII vaccinated group after challenge with DENV-infected K562 cells. Collectively, the results demonstrate that DENV-EDIII expressed in the inactivated ST strain could induce robust humoral and cell-mediated immunity specific to the target antigen and could provide significant protective potential.
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MEDLINE
Assunto principal:
Salmonella typhimurium
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Dengue
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Vírus da Dengue
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Vacinas contra Dengue
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article