Bernstein, David I.Wald, AnnaWarren, TerriFife, KennethTyring, StephenLee, PatriciaVan Wagoner, NickMagaret, AmaliaFlechtner, Jessica B.Tasker, SybilChan, JasonMorris, AmyHetherington, Seth2018-01-042018-01-042017Bernstein, D. I., Wald, A., Warren, T., Fife, K., Tyring, S., Lee, P., ... & Chan, J. (2017). Therapeutic Vaccine for Genital Herpes Simplex Virus-2 Infection: Findings From a Randomized Trial. The Journal of Infectious Diseases, 215(6), 856-864. https://doi.org/10.1093/infdis/jix004https://hdl.handle.net/1805/14942Background. Genital herpes simplex virus type 2 (HSV-2) infection causes recurrent lesions and frequent viral shedding. GEN-003 is a candidate therapeutic vaccine containing HSV-2 gD2∆TMR and ICP4.2, and Matrix-M2 adjuvant. Methods. Persons with genital herpes were randomized into 3 dose cohorts to receive 3 intramuscular doses 21 days apart of 10 µg, 30 µg, or 100 µg of GEN-003, antigens without adjuvant, or placebo. Participants obtained genital swab specimens twice daily for HSV-2 detection and monitored genital lesions for 28-day periods at baseline and at intervals after the last dose. Results. One hundred and thirty-four persons received all 3 doses. Reactogenicity was associated with adjuvant but not with antigen dose or dose number. No serious adverse events were attributed to GEN-003. Compared with baseline, genital HSV-2 shedding rates immediately after dosing were reduced with GEN-003 (from 13.4% to 6.4% for 30 μg [P < .001] and from 15.0% to 10.3% for 100 µg [P < .001]). Lesion rates were also significantly (P < .01) reduced immediately following immunization with 30 µg or 100 µg of GEN-003. GEN-003 elicited increases in antigen binding, virus neutralizing antibody, and T-cell responses. Conclusions. GEN-003 had an acceptable safety profile and stimulated humoral and cellular immune responses. GEN-003 at doses of 30 µg and 100 µg reduced genital HSV shedding and lesion rates.enPublisher Policygenital herpesherpes simplex virus type 2 infectiontherapeutic vaccineArticle