Immunological memory forms the basis of vaccination and despite the availability of several successful vaccines, we lack sufficient knowledge regarding the mechanisms behind generation of immune memory in humans. To elucidate how memory CD8 T cells develop in the course of a primary acute viral infection, I have been studying virus-specific CD8 T cells in volunteers vaccinated with the highly effective live attenuated yellow fever vaccine (strain YF-17D). YF-17D causes a short duration of viremia, generates a robust T cell and neutralizing antibody response and elicits long-term protection against infection with pathogenic yellow fever virus. Thus, studying vaccinees in a yellow fever non-endemic area such as the US provides an ideal system to ask fundamental questions regarding the generation, maintenance and qualities of human virus-specific memory CD8 T cells in a primary infection. Using flow cytometry, genomic and epigenetic analyses, this research is geared towards a detailed understanding of memory CD8 T cell generation and will contribute towards developing methods to manipulate and improve sub-optimal CD8 T cell responses. An additional focus of this research is to look for immune correlates indicative of an effective, long-lasting CD8 T cell response that would enable better vaccine development in infections such as HIV where cellular immunity is important.