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

• Published in: Open forum infectious diseases 2017-10, Vol.4 (suppl_1), p.S415-S416
• Main Authors: Dropulic, Lesia, Wang, Kening, Oestreich, Makinna, Pietz, Harlan, Garabedian, Doreen, Jegaskanda, Sinthujan, Dowdell, Kennichi, Nguyen, Hanh, Laing, Kerry, Koelle, David, Azose, Aaron, Hunsberger, Sally, Lumbard, Keith, Chen, Aiying, Chang, Lee-Jah, Phogat, Sanjay, Cohen, Jeffrey
• Format: Article
• Language: English
• Subjects: Abstracts
• ISSN: 2328-8957; 2328-8957
• DOI: 10.1093/ofid/ofx163.1041

Abstract 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, 15 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 vs. 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 vs. 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 with 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 with 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 Disclosures L. Dropulic, sanofi pasteur: Collaborator, Research support; K. Wang, sanofi pasteur: Collaborator, Research support; M. Oestreich, sanofi pasteur: Collaborator, Research support;