Bernstein David I, Wald Anna, Warren Terri, Fife Kenneth, Tyring Stephen, Lee Patricia, Van Wagoner Nick, Magaret Amalia, Flechtner Jessica B, Tasker Sybil, Chan Jason, Morris Amy, Hetherington Seth
Cincinnati Children's Hospital Medical Center, University of Cincinnati, Ohio, USA.
Vaccine and Fred Hutchinson Cancer Research Center, University of Washington, Seattle, USA.
J Infect Dis. 2017 Mar 15;215(6):856-864. doi: 10.1093/infdis/jix004.
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.
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.
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.
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.
NCT01667341 (funded by Genocea).
2型单纯疱疹病毒（HSV-2）感染可导致复发性损害及频繁的病毒脱落。GEN-003是一种候选治疗性疫苗，包含HSV-2 gD2∆TMR和ICP4.2以及Matrix-M2佐剂。
将生殖器疱疹患者随机分为3个剂量组，分别间隔21天接受3次肌内注射，剂量为10μg、30μg或100μg的GEN-003、不含佐剂的抗原或安慰剂。参与者每天获取两次生殖器拭子标本用于HSV-2检测，并在基线期及最后一剂后的不同间隔期对生殖器损害进行为期28天的监测。
134人接受了全部3剂。反应原性与佐剂有关，而与抗原剂量或剂量次数无关。未将严重不良事件归因于GEN-003。与基线相比，GEN-003给药后生殖器HSV-2脱落率立即降低（30μg组从13.4%降至6.4%[P <.001]，100μg组从15.0%降至10.3%[P <.001]）。用30μg或100μg的GEN-003免疫后，损害发生率也显著降低（P <.01）。GEN-003可引起抗原结合、病毒中和抗体及T细胞反应增加。
GEN-003具有可接受的安全性，可刺激体液免疫和细胞免疫反应。30μg和100μg剂量的GEN-003可降低生殖器HSV脱落率和损害发生率。
NCT01667341（由Genocea资助）
