Antibodies Are Not Required to a Protective Immune Response Against Dengue Virus Elicited in a Mouse Encephalitis Model

Virology. 2016 Jan;487:41-9. doi: 10.1016/j.virol.2015.10.006. Epub 2015 Oct 21.

Abstract

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.

Keywords: Antibodies; Dengue; Immune response; Nonstructural proteins; T lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aedes / virology
  • Animals
  • Antibodies, Viral / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Line
  • Dengue / immunology
  • Dengue / prevention & control
  • Dengue / virology
  • Dengue Virus / immunology*
  • Disease Models, Animal
  • Encephalitis, Viral / immunology
  • Encephalitis, Viral / prevention & control*
  • Encephalitis, Viral / virology
  • Immune Sera / immunology
  • Immunity, Cellular / immunology
  • Immunization, Passive
  • Lymphocyte Depletion
  • Macaca mulatta
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Viral Nonstructural Proteins / immunology

Substances

  • Antibodies, Viral
  • Immune Sera
  • Viral Nonstructural Proteins