To each 100 L of serum dilution 100 L of CVS (100 FFD50) was added and the plate to was incubated at 37 for 1 hour. 2 cytokine responses did not differ significantly among the intramuscular and intradermal routes of postexposure vaccination. The number of cells generating IFN- and IL-4 correlated significantly with the levels of RVNA. Conclusion 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. Keywords: Rabies, Rabies prophylaxis, Rabies vaccines, IFN gamma, IL4, Immune response Introduction Rabies is acute viral encephalitis caused by a highly neurotropic negative sense single stranded RNA computer virus belonging to the genus of the family Rhabdoviridae. Though it is 100% fatal it is preventable by instituting timely pre-exposure or postexposure vaccination. Currently cell-culture derived vaccines are administered globally to provide immunity against rabies along with timely wound washing and local infiltration of rabies immune globulins [1]. In recent times a number of cell culture based rabies vaccines have been shown to possess long standing security, immunogenicity and efficacy [2,3,4]. These vaccines are believed to induce strong humoral responses resulting in rabies computer virus neutralizing antibodies (RVNA) which neutralize the computer virus DS21360717 before it reaches the central nervous system (CNS) [5,6]. However, the role of rabies computer virus specific cell mediated immune responses are not yet clearly comprehended and may play a significant role in clearing the computer virus from your CNS [7]. Upon antigen DS21360717 encounter during viral infections, the naive CD4 T cells may either differentiate into a type 1 cytokine generating Th1 cells or type 2 cytokine generating Th2 cells, interleukin (IL)-17 secreting Th17 cells or follicular helper T (TFH) cells. The Th1 cells that are important for anti-viral immunity secrete type 1 panel of cytokines including interferon- (IFN-), IL-2, and tumor necrosis factor- (TNF-). These cells are known to promote conversation of CD8 T cells with dendritic cells and help B cells to produce high affinity Rabbit Polyclonal to GSK3beta and neutralizing antibodies [8,9]. The Th2 cells that secrete type 2 cytokines such as IL-4, IL-5, and IL-13 are known to be important for their helper activity to B cells for humoral immune responses; however, they are also known to inhibit protective responses and promote immunopathology during many viral infections [8,10]. There are a few studies which DS21360717 DS21360717 have resolved the induction of type 1 and type 2 cytokine responses following administration of viral vaccines and have shown that both arms of immune responses are induced after measles, hepatitis B, and influenza vaccines [11,12,13]. The immunogenicity and efficacy of cell culture derived anti-rabies vaccines have been evaluated generally by measuring the humoral responses by determining RVNA titers following vaccination by the standard intramuscular (IM) route. However, there is lack of knowledge with respect to type 1 and type 2 cellular cytokine responses following vaccination with cell culture rabies vaccines which are known to induce high levels of RVNA both by the IM and intradermal (ID) route. The World Health Organization (WHO) has recommended ID route of immunization for developing countries since 1992 [14]. In fact postexposure prophylaxis by ID vaccination could increase global supply of vaccine doses as well as reduce per person immunization cost [15]. In the last 3 decades, ID vaccination has been used extensively in some Asian countries thereby reducing the economic burden of rabies prophylaxis and contributing to a decline in the incidence of human rabies. We therefore wanted to determine if vaccination by ID route against rabies resulted in the induction of antigen specific cellular immune responses in addition to RVNA responses; whether an ID booster vaccine dose enhances rabies specific immune response and whether the route of immunization significantly affects these responses. Detection of cytokines such as IFN-, as a signature for type 1 response and IL-4 for the type 2 response, from antigen stimulated peripheral blood mononuclear cells (PBMCs) of vaccinated individuals is a valuable tool for analyzing cell mediated immune responses following vaccination. We hence undertook a study to compare the induction of the type 1 cytokine IFN-, and the type 2 cytokine IL-4, in PBMCs from individuals who received pre-exposure main anti-rabies vaccination with or without booster vaccination by ID route and postexposure vaccination by either the ID or IM route. We have also attempted.