1345. A Replication-Defective Herpes Simplex Virus (HSV)-2 Vaccine, HSV529, is Safe and Well-Tolerated in Adults with or without HSV Infection and Induces Significant HSV-2-Specific Antibody Responses in HSV Seronegative Individuals
Session: Poster Abstract Session: Herpes Zoster Vaccine
Friday, October 6, 2017
Room: Poster Hall CD
Background: We conducted a phase 1, randomized, double-blind, placebo-controlled trial of a replication-defective HSV-2 vaccine, HSV529 (deleted for UL5 and UL29), in 60 healthy adults aged 18 to 40 years.

Methods: Subjects were enrolled in groups of 20 from 3 serogroups: HSV1+ or -/HSV2+ (group 1), HSV1+/HSV2– (group 2), and HSV1-/HSV2– (group 3). At months 0, 1, and 6, fifteen subjects in each group received HSV529 intramuscularly and 5 subjects received placebo. The primary endpoint was the frequency of solicited injection site and systemic reactions from day 0 to 7 after each vaccination and unsolicited adverse events up to 6 months after the last dose.

Results:

89% of vaccine recipients experienced a mild to moderate solicited injection site reaction versus 47% of placebo recipients (P = 0.006, 95% CI 0.129, 0.676) that did not preclude additional doses. 64% of vaccine recipients experienced solicited systemic reactions versus 53% of placebo recipients (P = 0.44, 95% CI -0.179, 0.402). Two serious adverse events occurred in 2 participants and were assessed as unrelated to HSV529 administration. Serum neutralizing antibody titers significantly increased from baseline after 3 doses of HSV529 compared to placebo in group 3 only (P < 0.001). This increase persisted up to 6 months after the third dose of vaccine (P < 0.001). Serum and vaginal antibodies to HSV2 glycoprotein D (gD) also significantly increased after 3 doses of vaccine in group 3 subjects (P < 0.001 and P = 0.012, respectively). The mean vaginal gD titer after 3 doses was about one-third of the mean serum gD titer. In addition, the vaccine induced significant levels of HSV2-specific antibody dependent cellular cytotoxicity (ADCC) after 3 doses in group 3 subjects compared to placebo (P < 0.001). Vaccine-induced CD4 T-cell responses were detected in 46%, 27%, and 36% of subjects in groups 1, 2, and 3, respectively, one month after the third dose of vaccine. CD8 T-cell responses were detected in 8%, 18%, and 14% of subjects in groups 1, 2, and 3, respectively, at the same time point.

Conclusion: The HSV529 vaccine was safe, well-tolerated, and immunogenic, eliciting significant neutralizing, gD, and ADCC-mediating antibodies, and modest cellular immune responses in HSV seronegative individuals. NCT01915212

Lesia Dropulic, M.D.1, Kening Wang, M.D.1, Makinna Oestreich, B.A.2, Harlan Pietz, B.S.3, Doreen Garabedian, BSN, RN4, Sinthujan Jegaskanda, PhD5, Kennichi Dowdell, PhD1, Hanh Nguyen, B.S.1, Kerry Laing, PhD6, David Koelle, M.D.6, Aaron Azose, B.S.7, Sally Hunsberger, PhD8, Keith Lumbard, MS9, Aiying Chen, PhD10, Lee-Jah Chang, MD10, Sanjay Phogat, PhD10 and Jeffrey Cohen, M.D.1, (1)Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD, (2)University of Minnesota Medical School, Minneapolis, MN, (3)Weill Cornell Medical College, New York City, NY, (4)NIH, Bethesda, MD, (5)Peter Doherty Institute for Infection and Immunity, Melbourne, Australia, (6)University of Washington Medicine, Seattle, WA, (7)Vanderbilt University Medical School, Nashville, TN, (8)Biostatistics Research Branch, NIAID, Rockville, MD, (9)Clinical Research Directorate/Clinical Monitoring Research Program, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, MD, (10)Sanofi Pasteur, Swiftwater, PA

Disclosures:

L. Dropulic, Sanofi Pasteur: Collaborator , Research support

K. Wang, Sanofi Pasteur: Collaborator , Research support

M. Oestreich, Sanofi Pasteur: Collaborator , Research support

H. Pietz, Sanofi Pasteur: Collaborator , Research support

D. Garabedian, Sanofi Pasteur: Collaborator , Research support

S. Jegaskanda, None

K. Dowdell, Sanofi Pasteur: Collaborator , Research support

H. Nguyen, Sanofi Pasteur: Collaborator , Research support

K. Laing, Sanofi Pasteur: Research Contractor , payment for conducting T cell assays

D. Koelle, Sanofi Pasteur: Research Contractor , payment for conducting T cell assays

A. Azose, Sanofi Pasteur: Research Contractor , Payment for conducting T cell assays

S. Hunsberger, None

K. Lumbard, None

A. Chen, Sanofi Pasteur: Employee , Salary

L. J. Chang, Sanofi Pasteur: Employee , Salary

S. Phogat, Sanofi Pasteur: Employee , Salary

J. Cohen, None

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