Effects of Different Doses of GEN-003, a Therapeutic Vaccine for Genital Herpes Simplex Virus-2, on Viral Shedding and Lesions

Results of a Randomized Placebo-Controlled Trial

Nicholas Van Wagoner, Kenneth Fife, Peter A. Leone, David I. Bernstein, Terri Warren, Lori Panther, Richard M. Novak, Richard Beigi, John Kriesel, Stephen Tyring, William Koltun, Gregg Lucksinger, Amy Morris, Bin Zhang, Lisa K. McNeil, Sybil Tasker, Seth Hetherington, Anna Wald

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: GEN-003 is a candidate therapeutic vaccine for genital herpes simplex virus type 2 (HSV-2). We compared virologic and clinical impact of varying GEN-003 doses. Methods: Adults with symptomatic HSV-2 received placebo or GEN-003 (30 or 60 µg antigen with 25, 50, or 75 µg adjuvant). Viral shedding and lesion rates before vaccination were compared with those measured immediately after vaccination, then at weeks 29-33 and 53-57 after last dose. Results: Compared with baseline shedding rates, the rate ratios for viral shedding immediately after treatment were as follows: 0.82 (95% confidence interval [CI], 0.49-1.36), 30 µg antigen/25 µg adjuvant (30/25) dose; 0.64 (95% CI, 0.45-0.92), 30/50 dose; 0.63 (95% CI, 0.37-1.10), 30/75 dose; 0.56 (95% CI, 0.36-0.88), 60/25 dose; 0.58 (95% CI, 0.38-0.89), 60/50 dose; 0.45 (95% CI, 0.16-0.79), 60/75 dose; and 0.98 (95% CI, 0.76-1.26), placebo. Lesion rate reductions by GEN-003 ranged from 31% to 69%, but lesion rates also decreased among placebo recipients (62%). Reductions in shedding and lesion rate were durable for 12 months for the 60 µg antigen plus 50 or 75 µg adjuvant groups. No serious adverse events occurred with vaccination. Conclusions: The most efficacious vaccine combinations for GEN-003 were the 60 µg/50 µg and 60 µg/75 µg doses.

Original languageEnglish (US)
Pages (from-to)1890-1899
Number of pages10
JournalThe Journal of infectious diseases
Volume218
Issue number12
DOIs
StatePublished - Nov 5 2018

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Virus Shedding
Herpes Genitalis
Human Herpesvirus 2
Vaccines
Randomized Controlled Trials
Placebos
Confidence Intervals
Vaccination
Antigens
Therapeutics
Combined Vaccines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Effects of Different Doses of GEN-003, a Therapeutic Vaccine for Genital Herpes Simplex Virus-2, on Viral Shedding and Lesions : Results of a Randomized Placebo-Controlled Trial. / Van Wagoner, Nicholas; Fife, Kenneth; Leone, Peter A.; Bernstein, David I.; Warren, Terri; Panther, Lori; Novak, Richard M.; Beigi, Richard; Kriesel, John; Tyring, Stephen; Koltun, William; Lucksinger, Gregg; Morris, Amy; Zhang, Bin; McNeil, Lisa K.; Tasker, Sybil; Hetherington, Seth; Wald, Anna.

In: The Journal of infectious diseases, Vol. 218, No. 12, 05.11.2018, p. 1890-1899.

Research output: Contribution to journalArticle

Van Wagoner, N, Fife, K, Leone, PA, Bernstein, DI, Warren, T, Panther, L, Novak, RM, Beigi, R, Kriesel, J, Tyring, S, Koltun, W, Lucksinger, G, Morris, A, Zhang, B, McNeil, LK, Tasker, S, Hetherington, S & Wald, A 2018, 'Effects of Different Doses of GEN-003, a Therapeutic Vaccine for Genital Herpes Simplex Virus-2, on Viral Shedding and Lesions: Results of a Randomized Placebo-Controlled Trial', The Journal of infectious diseases, vol. 218, no. 12, pp. 1890-1899. https://doi.org/10.1093/infdis/jiy415
Van Wagoner, Nicholas ; Fife, Kenneth ; Leone, Peter A. ; Bernstein, David I. ; Warren, Terri ; Panther, Lori ; Novak, Richard M. ; Beigi, Richard ; Kriesel, John ; Tyring, Stephen ; Koltun, William ; Lucksinger, Gregg ; Morris, Amy ; Zhang, Bin ; McNeil, Lisa K. ; Tasker, Sybil ; Hetherington, Seth ; Wald, Anna. / Effects of Different Doses of GEN-003, a Therapeutic Vaccine for Genital Herpes Simplex Virus-2, on Viral Shedding and Lesions : Results of a Randomized Placebo-Controlled Trial. In: The Journal of infectious diseases. 2018 ; Vol. 218, No. 12. pp. 1890-1899.
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abstract = "Background: GEN-003 is a candidate therapeutic vaccine for genital herpes simplex virus type 2 (HSV-2). We compared virologic and clinical impact of varying GEN-003 doses. Methods: Adults with symptomatic HSV-2 received placebo or GEN-003 (30 or 60 µg antigen with 25, 50, or 75 µg adjuvant). Viral shedding and lesion rates before vaccination were compared with those measured immediately after vaccination, then at weeks 29-33 and 53-57 after last dose. Results: Compared with baseline shedding rates, the rate ratios for viral shedding immediately after treatment were as follows: 0.82 (95{\%} confidence interval [CI], 0.49-1.36), 30 µg antigen/25 µg adjuvant (30/25) dose; 0.64 (95{\%} CI, 0.45-0.92), 30/50 dose; 0.63 (95{\%} CI, 0.37-1.10), 30/75 dose; 0.56 (95{\%} CI, 0.36-0.88), 60/25 dose; 0.58 (95{\%} CI, 0.38-0.89), 60/50 dose; 0.45 (95{\%} CI, 0.16-0.79), 60/75 dose; and 0.98 (95{\%} CI, 0.76-1.26), placebo. Lesion rate reductions by GEN-003 ranged from 31{\%} to 69{\%}, but lesion rates also decreased among placebo recipients (62{\%}). Reductions in shedding and lesion rate were durable for 12 months for the 60 µg antigen plus 50 or 75 µg adjuvant groups. No serious adverse events occurred with vaccination. Conclusions: The most efficacious vaccine combinations for GEN-003 were the 60 µg/50 µg and 60 µg/75 µg doses.",
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T2 - Results of a Randomized Placebo-Controlled Trial

AU - Van Wagoner, Nicholas

AU - Fife, Kenneth

AU - Leone, Peter A.

AU - Bernstein, David I.

AU - Warren, Terri

AU - Panther, Lori

AU - Novak, Richard M.

AU - Beigi, Richard

AU - Kriesel, John

AU - Tyring, Stephen

AU - Koltun, William

AU - Lucksinger, Gregg

AU - Morris, Amy

AU - Zhang, Bin

AU - McNeil, Lisa K.

AU - Tasker, Sybil

AU - Hetherington, Seth

AU - Wald, Anna

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Y1 - 2018/11/5

N2 - Background: GEN-003 is a candidate therapeutic vaccine for genital herpes simplex virus type 2 (HSV-2). We compared virologic and clinical impact of varying GEN-003 doses. Methods: Adults with symptomatic HSV-2 received placebo or GEN-003 (30 or 60 µg antigen with 25, 50, or 75 µg adjuvant). Viral shedding and lesion rates before vaccination were compared with those measured immediately after vaccination, then at weeks 29-33 and 53-57 after last dose. Results: Compared with baseline shedding rates, the rate ratios for viral shedding immediately after treatment were as follows: 0.82 (95% confidence interval [CI], 0.49-1.36), 30 µg antigen/25 µg adjuvant (30/25) dose; 0.64 (95% CI, 0.45-0.92), 30/50 dose; 0.63 (95% CI, 0.37-1.10), 30/75 dose; 0.56 (95% CI, 0.36-0.88), 60/25 dose; 0.58 (95% CI, 0.38-0.89), 60/50 dose; 0.45 (95% CI, 0.16-0.79), 60/75 dose; and 0.98 (95% CI, 0.76-1.26), placebo. Lesion rate reductions by GEN-003 ranged from 31% to 69%, but lesion rates also decreased among placebo recipients (62%). Reductions in shedding and lesion rate were durable for 12 months for the 60 µg antigen plus 50 or 75 µg adjuvant groups. No serious adverse events occurred with vaccination. Conclusions: The most efficacious vaccine combinations for GEN-003 were the 60 µg/50 µg and 60 µg/75 µg doses.

AB - Background: GEN-003 is a candidate therapeutic vaccine for genital herpes simplex virus type 2 (HSV-2). We compared virologic and clinical impact of varying GEN-003 doses. Methods: Adults with symptomatic HSV-2 received placebo or GEN-003 (30 or 60 µg antigen with 25, 50, or 75 µg adjuvant). Viral shedding and lesion rates before vaccination were compared with those measured immediately after vaccination, then at weeks 29-33 and 53-57 after last dose. Results: Compared with baseline shedding rates, the rate ratios for viral shedding immediately after treatment were as follows: 0.82 (95% confidence interval [CI], 0.49-1.36), 30 µg antigen/25 µg adjuvant (30/25) dose; 0.64 (95% CI, 0.45-0.92), 30/50 dose; 0.63 (95% CI, 0.37-1.10), 30/75 dose; 0.56 (95% CI, 0.36-0.88), 60/25 dose; 0.58 (95% CI, 0.38-0.89), 60/50 dose; 0.45 (95% CI, 0.16-0.79), 60/75 dose; and 0.98 (95% CI, 0.76-1.26), placebo. Lesion rate reductions by GEN-003 ranged from 31% to 69%, but lesion rates also decreased among placebo recipients (62%). Reductions in shedding and lesion rate were durable for 12 months for the 60 µg antigen plus 50 or 75 µg adjuvant groups. No serious adverse events occurred with vaccination. Conclusions: The most efficacious vaccine combinations for GEN-003 were the 60 µg/50 µg and 60 µg/75 µg doses.

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