**5. Conclusions**

There is a great need for new approaches targeting EBV, against which there are no licensed vaccines or immunotherapies available. Acute infection can lead to infectious mononucleosis, and the risk of autoimmune diseases such as multiple sclerosis is increased following symptomatic infection. Immunotherapy targeting conserved, expressed, and oncogenic viral genes has the potential to drive immunity that impacts EBV-associated cancers. Here we generated synthetic DNA immunogens targeting the EBV latent proteins EBNA1, LMP1, and LMP2. These engineered SynCon DNA vaccines were delivered by Cellectra EP into mice to study their immune responses. The combination of immunogens generated significant CD8 T cell responses. In addition, these responses impacted tumor growth in a mouse challenge model. Further study of this combination synthetic DNA approach in EBV-driven disease is warranted.

**Author Contributions:** Conceptualization, A.P.-P., D.B.W. and K.W.; methodology, A.P.-P. and K.W.; validation, A.P.-P. and K.W.; formal analysis, A.P.-P. and K.W.; investigation, A.P.-P. and K.W.; data curation, A.P.-P. and K.W.; Writing—Original Draft preparation, K.W.; Writing—Review and Editing, A.P.-P., D.B.W. and K.W.; visualization, A.P.-P. and K.W.; supervision, D.B.W.; project administration, A.P.-P. and K.W.; funding acquisition, D.B.W.

**Funding:** This work was supported by a University of Pennsylvania/Wistar Institute NIH Special Program of Research Excellence grant (P50 CA174523 to D.B.W.), the Wistar National Cancer Institute Cancer Center (P30 CA010815), the W.W. Smith Family Trust (to D.B.W.), a grant from Inovio Pharmaceuticals (to D.B.W.), and T32 CA 9171-41 (K.W.).

**Acknowledgments:** We would like to thank the Wistar Flow Cytometry Facility and Animal Facility for their technical assistance.

**Conflicts of Interest:** D.B.W. has received an SRA, has an ownership interest including IP, and performs Board service for Inovio, has received an SRA from and consulted for GeneOne; has received an SRA from and consulted with Geneos; and has served on advisory boards for AstraZeneca and Sanofi, among others. A.P.-P. is an employee at Inovio Pharmaceuticals. The other authors declare no conflicts of interest.
