1343. Functional Antibody Responses to GEN-003, a Herpes Simplex Virus Immunotherapy that Durably Reduces Viral Shedding up to 12 Months Post Dosing
Session: Poster Abstract Session: Clinical Trials
Friday, October 28, 2016
Room: Poster Hall
Background: Over 16% of US adults are infected with Herpes Simplex Virus (HSV), the most common cause of genital ulcers worldwide. Recurrence and viral shedding rates vary widely. Data suggest that both B and T cell immunity are critical for control of reactivation of viral replication and disease but correlates of protection are unknown.

GEN-003 is a candidate immunotherapy containing two protein antigens, a deletion mutant of glycoprotein D (gD2ΔTMR) and a fragment of ICP4 (ICP4.2) combined with Matrix-M2 (MM; Novavax). In a Phase 2 clinical trial, GEN-003 significantly reduced viral shedding and lesion rates. Here we report antibody responses to GEN-003 and their correlation with viral shedding and lesion data through 1 year of follow up.

MethodsAdults (N=310) with symptomatic genital herpes were randomized to receive 3 intramuscular injections 3 weeks apart of GEN-003 at either 1 of 6 combinations of antigen and adjuvant, or placebo. Antibody responses were determined by capture ELISA and colorimetric HSV neutralization (NAb) assay at baseline and at intervals throughout the study. Viral shedding rate was determined by quantitative real-time PCR of genital swab samples collected twice daily for 28 day periods prior to and after the third dose, and at 6 and 12 months. Subjects recorded genital lesions, if present, daily.

Results: At 12 months, HSV-2 shedding was significantly reduced relative to baseline in 3 of 6 dose groups. The best dose levels, 60/50 and 60/75µg, resulted in 66% (p<0.0001) and 54% (p=0.01) viral shedding rate reduction and 65% (p=0.0033) and 47% (p=0.0165) genital lesion rate reduction, respectively. At these doses, mean IgG titers increased up to 21-fold to ICP4.2 and 8-fold to gD2ΔTMR and persisted 7- and 3-fold above baseline, respectively, at one year. Mean NAb titers increased over 5-fold and remained >2-fold over baseline at one year. gD2ΔTMR IgG and NAb titers correlated with viral copy number after the third dose (p<0.0001, Spearman’s rank correlations).

Conclusion:GEN-003 elicited increases in antigen-binding and NAb levels above baseline that persisted for at least one year after the last dose; consistent with viral shedding and lesion rate reduction. Antibody responses correlated with reduction in viral DNA copy number.

Lisa K. Mcneil, PhD1, Nicolle Siddall, BS1, Amy Baccari, BS1, Veronica Clemens, BS1, Johanna K. Kaufmann, PhD1, Shane Larson, MS1, Thomas Oliphant, MS, PhD2, Bin Zhang, PhD1, Jessica B. Flechtner, PhD1 and Seth Hetherington, MD1, (1)Genocea Biosciences, Cambridge, MA, (2)Innovative Analytics, Kalamazoo, MI

Disclosures:

L. K. Mcneil, Genocea Biosciences: Employee and Shareholder , Salary

N. Siddall, Genocea Biosciences: Employee and Shareholder , Salary

A. Baccari, Genocea Biosciences: Employee and Shareholder , Salary

V. Clemens, Genocea Biosciences: Employee and Shareholder , Salary

J. K. Kaufmann, Genocea Biosciences: Employee and Shareholder , Salary

S. Larson, Genocea Biosciences: Employee and Shareholder , Salary

T. Oliphant, Genocea Biosciences: Consultant , Consulting fee

B. Zhang, Genocea Biosciences: Employee and Shareholder , Salary

J. B. Flechtner, Genocea Biosciences: Employee and Shareholder , Salary

S. Hetherington, Genocea Biosciences: Employee and Shareholder , Salary

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