The circulation of flaviviruses, dengue (DEN), Japanese encephalitis ( JE) and West Nile (WN) viruses, and others, is generating a major concern in many countries. Both JE along with DEN have been endemic in large regions of India. WN virus infection, although circulating in southern regions for many years, in recent years, WN encephalitis patients have been demonstrated. While vaccines against JE have been developed and decrease outbreaks, in case of DEN and WN, vaccines are still in developing level, especially, it has been difficult to achieve the long-term protective immune response. The first licensed DEN vaccine, which is a live attenuated vaccine, was administered in countries where the virus is endemic, and has a potential to cause serious side effects, especially when administered to younger population as observed in the Philippines vaccination drive. In the case of WN, although the purified inactivated virion-based vaccine worked effectively as a veterinary vaccine for horses, no effective vaccine has yet been licensed for humans. The induction of CD4 + and CD8 + T cell responses is essential to complete protection by these viruses, as evidenced by responses to asymptomatic infections. Many studies have shown that neutralizing antibody (NAb) response is against surface structural proteins; CD4 + and CD8 + responses are mainly directed against nonstructural proteins rather than NAb response. New data suggest that encapsulating virus vaccines in nanoparticles (NPs) will direct antigen in cytoplasmic compartment by antigen-presenting cells, which will improve presentation to CD4 + and CD8 + T cells. Since tissue culture-derived, purified inactivated viruses are easier to manufacture and safer than developing live virus vaccines, inclusion of NP provides an attractive alternative for generating robust flaviviral vaccines that are affordable with long-lived protection.