2744. A Phase I Randomized, Observer-Blind, Controlled, Dose Escalation Trial of the Safety and Tolerability of a Single Intramuscular Dose of a PAL Adjuvant (Laboratory Code, FB-631) Co-administered with Seasonal TIV (2013–2014) to Healthy Adults ≥18–50 Years of Age

Abstract

BackgroundInactivated influenza vaccines (IV) efficacy is variable and sometimes poor. In this phase 1 trial the safety and immunogenicity of a novel nanoparticle adjuvant (Papaya Mosaic Virus (PapMV or PAL) at different dose levels combined with inactivated trivalent IV (TIV; FLUVIRAL® 2013–2014, GSK, Kirkland PQ) was assessed. Nonpathogenic in mammals, PAL is recognized as a pathogen-associated molecular pattern (PAMP) which stimulates innate, cell-mediated immunity (CMI) and adaptive immunity in naïve mice through activation of toll like receptor 7 and 8.MethodsHealthy persons 18–50 years of age were randomized to one of 6 study groups: 30 µg, 60 µg, 120 µg or 240 µg of PAL with 0.25 mL TIV, 240 µg of PAL with 0.125 mL TIV, or control (0.5 mL TIV). Solicited local and general adverse events (AE) were collected Day (D)0 to 6, unsolicited AE to D28, and serious AE to D1095. Hemagglutination-inhibition assays (HI), antibody to Influenza A virus nucleoprotein (NP), and peripheral blood mononuclear cells (PBMC) for measurement of interferon-gamma (IFNg) ELISPOT (response to PepMix influenza A H2N2 Ann Arbour NP, MP1, and an influenza peptide pool), granzyme B, and IFNg:IL:10 ratio were collected on D0, 7, 28, 120, and 180.ResultsThe most common solicited AEs were transient mild-to-moderate local pain (62.5%–87.5% of participants/group), drowsiness (≤37.5% of participants/group) and generalized muscle aches (12.5–50% of participants/group). There was one unrelated SAE. All participants had HI and anti-NP titers at baseline. HI GMTs increased at D28 post vaccine in most groups (Figure 1) and waned over time. HI fold Ab (Far) responses to TIV strains were poor in all groups (≤37.5% of participants/group had 4-Far to any strain). CMI results were consistent with humoral responses.ConclusionThe PAL adjuvant in doses of 30 to 240µg combined with reduced TIV dosages was safe with no signals up to 3 years after vaccine. Reduced doses of TIV co-presented with 240 µg PAL had similar HI GMTs as TIV. The CMI results suggest that the assessment of PAL efficacy on TIV immunization would have to be conducted in an influenza naïve population. DisclosuresScott Halperin, MD, GlaxoSmithKline: Ad hoc advisory boards, Other Financial or Material Support, Research Grant; Janssen Pharm: Research Grant; sanofi pasteur: Ad hoc advisory boards, Other Financial or Material Support, Research Grant.