title: Augmentation of cellular and humoral immune responses to HPV16 and HPV18 E6 and E7 antigens by VGX-3100.
abstract: We have previously demonstrated the immunogenicity of VGX-3100, a multicomponent DNA immunotherapy for the treatment of Human Papillomavirus (HPV)16/18-positive CIN2/3 in a phase 1 clinical trial. Here, we report on the ability to boost immune responses with an additional dose of VGX-3100. Patients completing our initial phase 1 trial were offered enrollment into a follow on trial consisting of a single boost dose of VGX-3100. Data show both cellular and humoral immune responses could be augmented above pre-boost levels, including the induction of interferon (IFN)γ production, tumor necrosis factor (TNF)α production, CD8+ T cell activation and the synthesis of lytic proteins. Moreover, observation of antigen-specific regulation of immune-related gene transcripts suggests the induction of a proinflammatory response following the boost. Analysis of T cell receptor (TCR) sequencing suggests the localization of putative HPV-specific T cell clones to the cervical mucosa, which underscores the putative mechanism of action of lesion regression and HPV16/18 elimination noted in our double-blind placebo-controlled phase 2B trial. Taken together, these data indicate that VGX-3100 drives the induction of robust cellular and humoral immune responses that can be augmented by a fourth "booster" dose. These data could be important in the scope of increasing the clinical efficacy rate of VGX-3100.
authors.affiliation: Inovio Pharmaceuticals , Plymouth Meeting, Pennsylvania, USA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Morrow
authors.affiliation: Inovio Pharmaceuticals , Plymouth Meeting, Pennsylvania, USA.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Kraynyak
authors.affiliation: Inovio Pharmaceuticals , Plymouth Meeting, Pennsylvania, USA.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Sylvester
authors.affiliation: Inovio Pharmaceuticals , Plymouth Meeting, Pennsylvania, USA.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Shen
authors.affiliation: Inovio Pharmaceuticals , Plymouth Meeting, Pennsylvania, USA.
authors.forename: Dinah
authors.initials: D
authors.lastname: Amante
authors.affiliation: Inovio Pharmaceuticals , Plymouth Meeting, Pennsylvania, USA.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Sakata
authors.affiliation: Unified Women's Clinical Research , Winston-Salem, North Carolina, USA.
authors.forename: Lamar
authors.initials: L
authors.lastname: Parker
authors.affiliation: Inovio Pharmaceuticals , Plymouth Meeting, Pennsylvania, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Yan
authors.affiliation: Inovio Pharmaceuticals , Plymouth Meeting, Pennsylvania, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: Boyer
authors.affiliation: Inovio Pharmaceuticals , Plymouth Meeting, Pennsylvania, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Roh
authors.affiliation: Inovio Pharmaceuticals , Plymouth Meeting, Pennsylvania, USA.
authors.forename: Laurent
authors.initials: L
authors.lastname: Humeau
authors.affiliation: Inovio Pharmaceuticals , Plymouth Meeting, Pennsylvania, USA.
authors.forename: Amir S
authors.initials: AS
authors.lastname: Khan
authors.affiliation: Inovio Pharmaceuticals , Plymouth Meeting, Pennsylvania, USA.
authors.forename: Kate
authors.initials: K
authors.lastname: Broderick
authors.affiliation: Inovio Pharmaceuticals , Plymouth Meeting, Pennsylvania, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Marcozzi-Pierce
authors.affiliation: Inovio Pharmaceuticals , Plymouth Meeting, Pennsylvania, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Giffear
authors.affiliation: Inovio Pharmaceuticals , Plymouth Meeting, Pennsylvania, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Lee
authors.affiliation: Johns Hopkins University School of Medicine , Baltimore, Maryland, USA.
authors.forename: Cornelia L
authors.initials: CL
authors.lastname: Trimble
authors.affiliation: Inovio Pharmaceuticals , Plymouth Meeting, Pennsylvania, USA.
authors.forename: J Joseph
authors.initials: JJ
authors.lastname: Kim
authors.affiliation: Inovio Pharmaceuticals , Plymouth Meeting, Pennsylvania, USA.
authors.forename: Niranjan Y
authors.initials: NY
authors.lastname: Sardesai
authors.affiliation: The Wistar Institute , Philadelphia, Pennsylvania, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
authors.affiliation: Inovio Pharmaceuticals , Plymouth Meeting, Pennsylvania, USA.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Bagarazzi