title: Cellular immune response following pre-exposure and postexposure rabies vaccination by intradermal and intramuscular routes.
abstract: OBJECTIVE
  Immunization against rabies in humans induces protective neutralizing antibodies; however, the induction of type 1 or type 2 cytokine mediated cellular immune responses following rabies vaccination is not understood. Hence, the present study investigated cellular cytokine responses in vaccinated individuals.
  
  
  METHODS
  The study groups included healthy rabies antigen naive controls (n=10), individuals who received intradermal primary (n=10) or booster pre-exposure vaccination (n=20) and subjects who received postexposure rabies vaccination either by intradermal (n=18) or intramuscular (n=20) routes. The antigen specific cellular responses were analyzed by stimulating peripheral blood mononuclear cells with a rabies vaccine antigen in the interferon-γ (IFN-γ) and interleukin-4 (IL-4) enzyme-linked immunospot (ELISpot) assay. These responses were compared to the rabies virus neutralizing antibody (RVNA) titers that were measured by rapid fluorescent focus inhibition test.
  
  
  RESULTS
  We observed that cellular and humoral immune responses to primary intradermal rabies vaccination could be greatly enhanced by a booster vaccine; and both type 1 and type 2 cytokine responses were significantly elevated. The magnitude of type 1 and type 2 cytokine responses did not differ significantly among the intramuscular and intradermal routes of postexposure vaccination. The number of cells producing IFN-γ and IL-4 correlated significantly with the levels of RVNA.
  
  
  CONCLUSIONS
  Both type 1 and type 2 cellular cytokine responses are strongly induced after rabies vaccination and directly correlate with levels of RVNA titers. The neutralizing antibody as well as the type 1 and type 2 cytokine responses may be important for vaccine induced protective responses against rabies.
authors: Deptartment of Neurovirology, National Institute of Mental Health and Neurosciences, Bangalore, India.
authors: Manjunatha Muniswamappa
authors: 0000-0003-3908-7222
authors: MM
authors: Venkataswamy
authors: Deptartment of Neurovirology, National Institute of Mental Health and Neurosciences, Bangalore, India.
authors: Shampur Narayan
authors: SN
authors: Madhusudana
authors: Deptartment of Neurovirology, National Institute of Mental Health and Neurosciences, Bangalore, India.
authors: Sampada Sudarshan
authors: SS
authors: Sanyal
authors: Deptartment of Neurovirology, National Institute of Mental Health and Neurosciences, Bangalore, India.
authors: Shaheen
authors: S
authors: Taj
authors: Deptartment of Neurovirology, National Institute of Mental Health and Neurosciences, Bangalore, India.
authors: Ashwin Yajaman
authors: AY
authors: Belludi
authors: Deptartment of Neurovirology, National Institute of Mental Health and Neurosciences, Bangalore, India.
authors: Reeta Subramaniam
authors: RS
authors: Mani
authors: Deptartment of Neurovirology, National Institute of Mental Health and Neurosciences, Bangalore, India.
authors: Nandita
authors: N
authors: Hazra
keywords: IFN gamma; IL4; Immune response; Rabies; Rabies prophylaxis; Rabies vaccines
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