Screening for T cell-eliciting proteins of Japanese encephalitis virus in a healthy JE-endemic human cohort using recombinant baculovirus-infected insect cell preparations

Abstract

The analysis of cell-mediated immune responses in virus-exposed but healthy individuals may contribute to define the features of the T cell response associated with resistance. We report, for the first time, on adaptive T cell responses to 5 largest of the 10 proteins that together constitute 76% of the coding potential of the Japanese encephalitis virus (JEV) genome in a naturally exposed healthy JE-immune human cohort. Fixed and sonified whole cell preparations of insect cells individually expressing recombinant prM, E, NS1, NS3 and NS5 proteins of JEV were used in vitro to stimulate lymphocytes from individuals who had experienced subclinical JEV infections. NS3-specific memory T cells were detected in up to 86% of the JEV-infected cohort whereas prM, E and NS1 each elicited reactions in approximately 45% among individuals tested, suggesting that NS3 is an important target for JEV-specific cell-mediated immune responses. Responses to NS5, the largest viral protein were in contrast the poorest, seen in only 13% of the cohort. Moreover, NS3 stimulated interferon-gamma production in both CD4(+) and CD8(+) T cells indicating that a Th1 immune response to the NS3 protein may be a critical determinant of immune control of JEV infection.

Comparative Efficacies of Three Commercially Available Vaccines against West Nile Virus (WNV) in a Short-Duration Challenge Trial Involving an Equine WNV Encephalitis Model

“…Modified live vaccines, such as CP-WN and WN-FV, should be capable of the induction of cell-mediated immunity in addition to humoral immunity. The importance of cellmediated immunity (T-helper response and cytotoxic T cells) and memory T cells in the protection against WNV and other related flaviviruses has been demonstrated in experimental murine studies (7,24) and field studies characterizing populations among whom flavivirus is endemic (Japanese encephalitis and dengue fever) (13,27). Characterization of the protective immune responses to equine WNV vaccines has not been studied for horses due to the limitations of the previous mosquito and needle inoculation challenge models combined with the limited availability of equine-specific immunologic reagents.…”

Immunization with recombinant adenovirus synthesizing the secretory form of Japanese encephalitis virus envelope protein protects adenovirus-exposed mice against lethal encephalitis

“…In the present work we also observed high levels of IFN-c synthesis by splenocytes of the RAdEsimmunized mice. This may contribute to the high levels of protection seen in RAdEs-immunized mice as IFN-c production by the T cells was found to be a critical determinant for immune control of JEV infection [58,59].…”

Japanese encephalitis virus produces a CD4+ Th2 response and associated immunoprotection in an adoptive-transfer murine model

“…The increased proliferation of CD4 + T cells in response to live virus compared with inactivated antigen might be because of T-cell responses elicited towards the non-structural proteins of live JEV. Kumar et al (2003) identified the NS3 protein of JEV as a dominant CD4…”