Comparative Analysis of Cellular Immunogenicity between Japanese Encephalitis (JE) Vaccine Non Responder and High Antibody Titer Group in JE Endemic Area of Northern India

Background:Japanese Encephalitis (JE) is the leading cause of viral encephalitis in Asia. Vaccination is the most effective countermeasure for protecting individuals from Japanese Encephalitis virus (JEV) infection. Vaccine-mediated immunity is often multifactorial and the best protection is likely to be elicited by the combination of strong humoral and cell-mediated immune responses. Role of T cell in protection against JEV infection were previously reported. However, neutralizing antibodies and its persistence after JEV vaccination is considered as important correlate of protection following JEV infection. Despite the excessive research covering the humoral response after Japanese encephalitis infection or vaccination, role played by cellular immunity is largely unknown. Thus this study was undertaken to investigate contribution of T cell response in antibody generation.

Methods: Children of 1-15 years of age received single dose of live attenuated SA-14-14-2 JE vaccine under JE vaccination drive (April 2014 to May 2014) were enrolled for this study. Blood samples from 149 children were collected on day 0 (pre- vaccination) and day 28 post-vaccination. Neutralizing anti-JE virus antibody titer were assessed in serum by plaque reduction neutralization test (PRNT). Further percentage of T cell subset CD3⁺_, CD8⁺, CD4⁺ IFN-γ⁺ , CD4⁺ IL-4⁺, CD4⁺ IL-17⁺and CD4⁺CD25⁺ T_Reg in children belongs to non responders and high titer group were determined by flow cytometry. Plasma level of various cytokine IFN- γ, IL-4, IL-17, TGF-β and IL-10 were measured by ELISA

Results:23(15.43 %) children were found to be non responder (PRNT <10) and 30 (20.13%) were found to be of high antibody titer group (PRNT>320). Higher percentage of Treg cell was found in non responder (2.44± 0.19%) when compare to high titer group (0.812± 0.14%) ( p<0.001). Moreover significant increased expression of TGF-β was also found in non responder than high titer group. (p=0.002).

Conclusion:This study indicates that Treg cells expansion have role in down regulating the antibody response to Japanese Encephalitis vaccination. Increased expression of TGF-β in non responder seems to stimulate additional Treg production. Further studies are needed to evaluate if removing dominant Treg epitopes could improve the immunogenicity and developing an effective JE vaccine strategy in future.