A DNA vaccine candidate encoding the structural prM/E proteins elicits a strong immune response and protects mice against dengue-4 virus infection.
A DNA vaccine expressing dengue-4 virus premembrane (prM) and envelope (E) genes was produced by inserting these genes into a mammalian expression plasmid (pCI). Following a thorough screening, including confirmation of protein expression in vitro, a recombinant clone expressing these genes was selected and used to immunize BALB/c mice. After 3 immunizations all the animals produced detectable levels of neutralizing antibodies against dengue-4 virus. The cytokines levels and T cell proliferation, detected ex vivo from the spleen of the immunized mice, showed that our construction induced substantial immune stimulation after three doses. Even though the antibody levels, induced by our DNA vaccine, were lower than those obtained in mice immunized with dengue-4 virus the levels of protection were high with this vaccine. This observation is further supported by the fact that 80% of the vaccine immunized group was protected against lethal challenge. In conclusion, we developed a DNA vaccine employing the genes of the prM and E proteins from dengue-4 virus that protects mice against this virus.
Laboratory of Molecular Virology, Department of Clinical Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Danielle Malta
DM
Lima
Sérgio Oliveira
SO
de Paula
Rafael Freitas de Oliveira
RF
França
Patrícia V B
PV
Palma
Fabiana R
FR
Morais
Alessandra Cristina
AC
Gomes-Ruiz
Maria Teresa Prudente
MT
de Aquino
Benedito Antonio Lopes
BA
da Fonseca
D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D049109:Cell Proliferation; D003715:Dengue / Q000517:prevention & control*; D003716:Dengue Virus / Q000235:genetics* / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors; D007117:Immunization, Secondary / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids; D013154:Spleen / Q000276:immunology; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D015678:Viral Structural Proteins / Q000235:genetics* / Q000276:immunology*
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019444:Vaccines, DNA; D015678:Viral Structural Proteins