2. Frequency and severity of i njection site reactions including administration site pain, skin erythema, induration, bleeding, tenderness and infection. 3.2.2 Secondary Endpoint The secondary endpoints is immune response after immun otherapy based on correlative measures: 1. Measure HPV -16 and HPV -18 specific antibody levels . A standardized binding ELISA will be performed to measure the anti –HPV16/18 E6 or E7 antibody response induced by VGX-3100 and INO -9012. 96- well enzyme immunoassay plates will be coated with HPV16 or HPV18 E6 or E7 proteins (1 μg/ml) (recombinant HPV16/18 E7 and HPV16 E6 procured from ProteinX Lab, HPV18 E6 from Impact Biologicals ). Subject s era will be diluted with 1% bovine serum albumin in PBS and tested in tripl icate with an automated and calibrated plate washer and read on a kinetic microplate reader (Molecular Devices). Samples will be scored as positive if the average optical density (OD) was greater than 0.15 absorbance units and greater than the average OD b efore preimmunization plus 2.5 times the standard deviation of the OD compared to corresponding preimmunized samples at the same dilution. 2. Using Antige n-specific IFN -γ ELISpot assays, determine the number of antigen- specific spot forming units (SFU) in response to stimulation with HPV16 and HPV18 . T cell responses will be assessed using an HPV IFN-γ ELISpot assay . PBMCs will be thawed and plated at 200,000 cells/well. Cells will be incubated with HPV16 and HPV18 peptides corresponding to E6 and E7 proteins of HPV . The three sets of peptides, each contain 15– amino acid residues overlapping by 8 amino acids representing the entire consensus E6/E7 fusion protein sequence of HPV16 or HPV18, and are pooled at a concentration of 2 μg/ml per peptide into two pools [ 12]. After an overnight incubation, IFN -gamma release will be detected using standard procedures. The average number of SFU counted in R10 wells will be subtracted from the average in individual HPV peptide wells and then adjusted to 1 × 10 6 PBMCs for each HPV peptide pool. Additionally, PBMC responses against a pool of known antigenic epitopes combined from Cytomegalovirus, Epstein Barr Virus and Influenza (CEF) will be tested in order to track general cellular immune competence during the study in the same manner as HPV responses described above. 3. Evaluate cytotoxic T cells in response to HPV specific immunotherapy by flow cytometry . Additional assessment of cellular immune activity will occur via the application Flow Cytometry. Flow Cytometric assays will include an examination the influence of immunotherapy on the ability of patient T cells to exhibit phenotypic markers associated 26 Date: 8 April 2016 v 2.1 INO-3112 UPCC # 39313 / Inovio HPV -005 Inovio Pharmaceuticals, Inc Clinical Protocol with cytolytic potential after short- term stimulation by HPV E6 and E7 of VGX -3100 antigen (hereafter referred to as “CTL Phenotyping”), the ability of patient T cells to remain active in the presence of long -term anti gen exposure and efficiently synthesize proteins used in lytic activity (hereafter referred to as “Lytic Granule Loading”) and the ability of patient T cells to effectively employ Granzyme B for the purposes of lytic degranulation and killing of target cel ls expressing HPV E6 and E7 (hereafter referred to as “Killing”). These panels may vary as newer information becomes available within the literature. i. The assay for CTL Phenotyping will employ a 6 -hour in vitro stimulation of unfractionated patient PBMCs using peptides spanning VGX-3100 antigens as described above, an irrelevant peptide control (OVA) and a positive control (Staphylococcal Enterotoxin B or a combination of phorbol 12- myristate 13 - acetate and Ionomycin). The CTL Phenotyping assay will examin e the following external cellular markers: CD3, CD4, CD8 (T cell identification), CD45RO, CCR7 (memory subset identification), and CD107a. The CTL Phenotyping assay will additionally analyze the following intracellular markers: Interferon Gamma (Th1 biasi ng cytokine), Tumor Necrosis Factor Alpha, Granzyme A, Granzyme B and Perforin (proteins involved in lytic degranulation and cytotoxic potential ). This panel of markers may vary as new information becomes available. ii. The Lytic Granule Loading assay will emp loy a 120-hour in vitro stimulation of unfractionated patient PBMCs using peptides spanning VGX-3100 antigens, an irrelevant peptide control (OVA) and a positive control (Concanavalin A). The Lytic Granule Loading assay will examine the following external cellular markers: CD3, CD4, CD8 (T cell identification), and CD137 (also known as 41BB – marker of T cell activation). The Lytic Granule Loading assay will additionally analyze the following intracellular markers: Granzyme A, Granzyme B , Granulysin and Perforin (proteins involved in lytic degranulation and cytotoxic potential). This panel of markers may vary as new information becomes available.