Objectives: This work describes a non-human primate immunogenicity study and the humoral and cellular response for the YFE antigen as part of the development of a subunit vaccine against the Yellow Fever envelope (E) protein utilizing the plant-based expression platform. Methods: This study included 20 animals and two formulations (one each of YF-E alone and fusion to lichenase) were selected based on immunogenicity studies in mice. Monkeys were immunized intramuscularly with 30 µg of YFE-1T

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... YFE-2 plus Alhydrogel TM three times at 30-days interval. One group was immunized intramuscularly with a single dose of 17DD vaccine. The Neutralizing Antibody Titers (Log 10 mIU/mL) were assayed by PRNT 30, 60, 90 days after first immunization and after challenge with 17DD vaccines in all groups (104 DPI). Viremia and RNAemia after challenge of all groups were assayed by titration and qPCR. We also measured yield of total IgG against yellow fever E protein; Avidity Index (AI) of IgG antibodies against E protein in rhesus sera; and magnitude of cellular immune response against E protein measured by IFN- -ELISpot. The Functional profile of CD4+ T cell and CD8+ T cell responses after challenge with 17DD in rhesus monkeys vaccinated with YF 17DD, YFE-1T and YFE-2E was assessed. We carried out multi-parameter ICS at day 104 (14 days after challenge with YF 17DD virus) to determine the ability of protein E-specific CD4 + T-cells and CD8 + T-cells to degranulate (CD107a) and secrete IFN-γ, TNF-α,and/or IL-2. The antigen stimuli in this assay consisted of recombinant E protein at 20 µg/mL. Results and Conclusion: All monkeys seroconvert after the second dose of YFE-1T and YFE2E. After challenge, viremia could be detected in 3 animals inoculated with