1655. Significant Neutralizing Antibody and Cytolytic T Cell Responses to GEN-003, a Herpes Simplex Virus Immunotherapy, in a Phase 2b Study
Session: Poster Abstract Session: Viral Treatment and Prevention
Friday, October 6, 2017
Room: Poster Hall CD
Background: Over 500 million people globally have genital ulcerative disease due to herpes simplex virus (HSV). Data suggest that both B- and T-cell immune responses are critical for effective control of viral replication and disease symptoms. GEN-003 is a potential immunotherapy containing two recombinant HSV-2 proteins, ICP4.2 and gD2ΔTMR combined with adjuvant, Matrix-M2™ (MM2, Novavax). In a Phase 2 clinical trial, GEN-003 resulted in a reduction in viral shedding and lesion rates. Here we report immunogenicity responses to GEN-003 through 1 year of follow up.

Methods: In total, 131 adults with clinically diagnosed HSV-2 infection were randomly assigned to one of two GEN-003 dose groups (60 µg of antigens with either 50 or 75 µg MM2 adjuvant) or placebo. Subjects were immunized three times at 21-day intervals. Serum was collected on days 1, 22, 43, and 71, and at 6 and 12 months. Heparinized whole blood for peripheral blood mononuclear cell enrichment was collected on days 1, 8, and 50, and at 6 and 12 months. Humoral responses were evaluated by indirect IgG ELISA and a cell-based colorimetric HSV-2 neutralizing antibody assay. Cellular responses were evaluated by an interferon-γ (IFN-γ)/Granzyme B (GrB) fluorescent enzyme-linked immunospot assay.

Results: Following the first immunization, mean IgG titers to ICP4.2 and gD2ΔTMR increased >60-fold and >8-fold from baseline, respectively, in both GEN-003 dose groups. Elevated antibody levels persisted above 8-fold through Day 71. Mean neutralizing antibody titers were >4-fold higher versus baseline at Day 71 for both dose groups. Increases in IFN-γ, GrB, and dual-secreting T-cell responses to both vaccine antigens peaked at Day 8 post-first immunization and were sustained through Day 50 for the 60 µg GEN-003 antigens/50 µg MM2 group. T-cell responses in the 60 µg GEN-003 antigens/75 µg MM2 group peaked at Day 8 and decreased thereafter. Placebo group values did not increase from baseline for all above parameters. Further evaluation of immunogenicity at the 6 and 12-month time points will be examined.

Conclusion: Overall, immunization of HSV-2 infected subjects with GEN-003 induced both cellular and humoral immune responses that may play a role in controlling both viral shedding and symptoms of genital disease.

Lisa K. McNeil, PhD1, Amy Baccari, BS1, Veronica Clemens, BS1, David Dominguez, BS1, Tyler Fenske, BS1, Thomas Oliphant, MS, PhD2, James Perry, BA1, Nicolle Siddall, BS1, Jin Yuan, PhD1, Thomas Heineman, MD, PhD1, Seth Hetherington, MD1 and Jessica B. Flechtner, PhD1, (1)Genocea Biosciences, Cambridge, MA, (2)Innovative Analytics, Kalamazoo, MI

Disclosures:

L. K. McNeil, Genocea Biosciences: Employee , Salary

A. Baccari, Genocea Biosciences: Employee , Salary

V. Clemens, Genocea Biosciences: Employee , Salary

D. Dominguez, Genocea Biosciences: Employee , Salary

T. Fenske, Genocea Biosciences: Employee , Salary

T. Oliphant, Genocea Biosciences: Consultant , Consulting fee

J. Perry, Genocea Biosciences: Employee , Salary

N. Siddall, Genocea Biosciences: Employee , Salary

J. Yuan, Genocea Biosciences: Employee , Salary

T. Heineman, Genocea Biosciences: Employee , Salary

S. Hetherington, Genocea Biosciences: Employee , Salary

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

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