title: Immune responses elicited by the GEN-003 candidate HSV-2 therapeutic vaccine in a randomized controlled dose-ranging phase 1/2a trial.
abstract: GEN-003 is a candidate therapeutic HSV-2 vaccine containing a fragment of infected cell protein 4 (ICP4.2), a deletion mutant of glycoprotein D2 (gD2ΔTMR), and Matrix-M2 adjuvant. In a dose-ranging phase 1/2a clinical trial, immunization with GEN-003 reduced viral shedding and the percentage of reported herpetic lesion days. Here we examine the immune responses in the same trial, to characterize vaccine-related changes in antibody and cell-mediated immunity.
  
  
  
  Participants with genital HSV-2 infection were randomized to 1 of 3 doses of GEN-003, antigens without adjuvant, or placebo. Subjects received 3 intramuscular doses, three weeks apart, and were monitored for viral shedding, lesions and immunogenicity. Antibody titers were measured by ELISA and neutralization assay in serum samples collected at baseline and 3weeks post each dose. T cell responses were assessed pre-immunization and 1week post each dose by IFN-γ ELISpot and intracellular cytokine staining. Blood was also collected at 6 and 12months to monitor durability of immune responses.
  
  
  
  Antibody and T cell responses increased with vaccination and were potentiated by adjuvant. Among the doses tested, the rank order of reduction in viral shedding follows the ranking of fold change from baseline in T cell responses. Some immune responses persisted up to 12months.
  
  
  
  All measures of immunity are increased by vaccination with GEN-003; however, a correlate of protection is yet to be defined.
authors.affiliation: Genocea Biosciences, Inc., Cambridge, MA, USA. Electronic address: jessica.flechtner@genocea.com.
authors.forename: Jessica Baker
authors.initials: JB
authors.lastname: Flechtner
authors.affiliation: Genocea Biosciences, Inc., Cambridge, MA, USA.
authors.forename: Deborah
authors.initials: D
authors.lastname: Long
authors.affiliation: Genocea Biosciences, Inc., Cambridge, MA, USA.
authors.forename: Shane
authors.initials: S
authors.lastname: Larson
authors.affiliation: Genocea Biosciences, Inc., Cambridge, MA, USA.
authors.forename: Veronica
authors.initials: V
authors.lastname: Clemens
authors.affiliation: Genocea Biosciences, Inc., Cambridge, MA, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Baccari
authors.affiliation: Genocea Biosciences, Inc., Cambridge, MA, USA.
authors.forename: Lena
authors.initials: L
authors.lastname: Kien
authors.affiliation: Genocea Biosciences, Inc., Cambridge, MA, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Chan
authors.affiliation: Genocea Biosciences, Inc., Cambridge, MA, USA.
authors.forename: Mojca
authors.initials: M
authors.lastname: Skoberne
authors.affiliation: Genocea Biosciences, Inc., Cambridge, MA, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Brudner
authors.affiliation: Genocea Biosciences, Inc., Cambridge, MA, USA.
authors.forename: Seth
authors.initials: S
authors.lastname: Hetherington
mesh_terms: D000276:Adjuvants, Immunologic; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D004306:Dose-Response Relationship, Immunologic; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology* / Q000628:therapy*; D022301:Herpes Simplex Virus Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007167:Immunotherapy; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology; D014763:Viral Matrix Proteins / Q000008:administration & dosage / Q000276:immunology; D017201:Virus Shedding; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D022301:Herpes Simplex Virus Vaccines; D008562:Membrane Glycoproteins; D014763:Viral Matrix Proteins; D007371:Interferon-gamma
keywords: Herpes simplex virus; Immune response; Immunotherapy; Vaccine