The immunotherapeutic GEN-003 as a prophylactic vaccine candidate for genital herpes in guinea pigs

Abstract

Abstract GEN‑003 is a subunit vaccine candidate containing adjuvanted gD and ICP4 antigens that has shown durable therapeutic efficacy against genital herpes in a phase 2 clinical trial. Here we describe the potential benefit of GEN-003 as a prophylactic vaccine in a guinea pig model of genital herpes. Animals were immunized three times every two weeks with GEN-003 or control and intravaginally challenged with herpes simplex virus 2 (HSV-2, MS strain) 21 days later. GEN-003 significantly reduced frequency and severity of genital lesions in both acute and early stages of recurrent infection by over 85%, and 60% of vaccinated guinea pigs did not develop any lesions during the 33 day follow-up period. Furthermore, viral genome copy numbers recovered in vaginal swabs from GEN-003-immunized animals were 100-fold lower than from controls. Recurrent shedding frequencies were reduced by 27%. GEN-003 vaccination induced antigen-specific antibody responses at least as strong as those elicited by viral infection. Driven by gD-specific antibodies, HSV-2 neutralizing antibody titers followed the same pattern. After viral challenge, peripheral antigen-specific T cell responses in spleens of GEN-003-immunized animals were lower than those in controls, as measured by interferon-γ ELISpot. This might have resulted from increased antigen-specific T cell recruitment to the genital mucosa, or decreased exposure to the virus due to fewer recurrences. Additional methods to better understand mucosal mechanisms of protection are in development. In summary, GEN-003 shows promise as a prophylactic vaccine candidate for genital herpes. Ongoing studies will determine if protection can be further enhanced by addition or exchange of antigens and/or adjuvants.