Antibodies are not required to a protective immune response against dengue virus elicited in a mouse encephalitis model.
Generating neutralizing antibodies have been considered a prerequisite to control dengue virus (DENV) infection. However, T lymphocytes have also been shown to be important in a protective immune state. In order to investigate the contribution of both humoral and cellular immune responses in DENV immunity, we used an experimental model in which a non-lethal DENV2 strain (ACS46) is used to intracranially prime Balb/C mice which develop protective immunity against a lethal DENV2 strain (JHA1). Primed mice generated envelope-specific antibodies and CD8(+) T cell responses targeting mainly non-structural proteins. Immune sera from protected mice did not confer passive protection to naïve mice challenged with the JHA1 strain. In contrast, depletion of CD4(+) and CD8(+) T lymphocytes significantly reduced survival of ACS46-primed mice challenged with the JHA1 strain. Collectively, results presented in this study show that a cellular immune response targeting non-structural proteins are a promising way in vaccine development against dengue.
Laboratório de Desenvolvimento de Vacinas, Departamento de Microbiologia, Universidade de São Paulo, Brasil. Electronic address: jhamorim@usp.br.
Jaime Henrique
JH
Amorim
Laboratório de Desenvolvimento de Vacinas, Departamento de Microbiologia, Universidade de São Paulo, Brasil.
Rúbens Prince
RP
dos Santos Alves
Laboratório de Desenvolvimento de Vacinas, Departamento de Microbiologia, Universidade de São Paulo, Brasil.
Raíza
R
Bizerra
Laboratório de Desenvolvimento de Vacinas, Departamento de Microbiologia, Universidade de São Paulo, Brasil.
Sara
S
Araújo Pereira
Laboratório de Desenvolvimento de Vacinas, Departamento de Microbiologia, Universidade de São Paulo, Brasil.
Lennon
L
Ramos Pereira
Laboratório de Desenvolvimento de Vacinas, Departamento de Microbiologia, Universidade de São Paulo, Brasil.
Denicar Lina
DL
Nascimento Fabris
Laboratório de Desenvolvimento de Vacinas, Departamento de Microbiologia, Universidade de São Paulo, Brasil.
Robert Andreata
RA
Santos
Instituto de Medicina Tropical de São Paulo e Faculdade de Medicina, Departamento de Moléstias Infecciosas e Parasitárias (LIMHC), Universidade de São Paulo, Brasil.
Camila Malta
CM
Romano
Laboratório de Desenvolvimento de Vacinas, Departamento de Microbiologia, Universidade de São Paulo, Brasil. Electronic address: lcsf@usp.br.
Luís Carlos
LC
de Souza Ferreira
D000330:Aedes / Q000821:virology; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D003715:Dengue / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D003716:Dengue Virus / Q000276:immunology*; D004195:Disease Models, Animal; D018792:Encephalitis, Viral / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D007106:Immune Sera / Q000276:immunology; D007111:Immunity, Cellular / Q000276:immunology; D007116:Immunization, Passive; D008212:Lymphocyte Depletion; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D017361:Viral Nonstructural Proteins / Q000276:immunology
D000914:Antibodies, Viral; D007106:Immune Sera; D017361:Viral Nonstructural Proteins
Antibodies; Dengue; Immune response; Nonstructural proteins; T lymphocytes