Recombinant nucleocapsid-like particles from dengue-2 virus induce protective CD4+ and CD8+ cells against viral encephalitis in mice.
Virus-like particles are a highly effective type of subunit vaccine that mimics the overall structure of virus particles without containing infectious genetic material. In this work, a particulate form of the recombinant capsid protein from dengue-2 was evaluated in mice to determine the level of protection against viral challenge and to measure the antigen-induced cell-mediated immunity (CMI). The nucleocapsid-like particles (NLPs) adjuvanted with alum did not induce antiviral antibodies. However, splenocytes from the immunized animals secreted high levels of IFN-gamma upon virus stimulation, and a significant protection rate was achieved after challenge with lethal dengue-2 virus. Finally, both IFN-gamma secretion and protection against viral encephalitis were demonstrated to be dependent on CD4(+) and CD8(+) cells. This study provides new evidences regarding the protective role of the CMI in the mouse model without the induction of neutralizing antibodies. Further studies in non-human primates or humanized mice should be carried out to elucidate the usefulness of the NLPs as a potential vaccine candidate against dengue disease.
Gil
Lázaro
L
Vaccines Division, Center for Genetic Engineering and Biotechnology, Playa, Havana, Cuba. lazaro.gil@cigb.edu.cu
López
Carlos
C
Lazo
Laura
L
Valdés
Iris
I
Marcos
Ernesto
E
Alonso
Ruby
R
Gambe
Ailyn
A
Martín
Jorge
J
Romero
Yaremis
Y
Guzmán
María G
MG
Guillén
Gerardo
G
Hermida
Lisset
L
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D003715:Dengue / Q000276:immunology / Q000517:prevention & control*; D053059:Dengue Vaccines / Q000276:immunology*; D003716:Dengue Virus / Q000276:immunology*; D004195:Disease Models, Animal; D018792:Encephalitis, Viral / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007115:Immunization Schedule; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D019251:Nucleocapsid / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology
D000914:Antibodies, Viral; D053059:Dengue Vaccines; D011994:Recombinant Proteins; D007371:Interferon-gamma