Phase III: Randomized observer-blind trial to evaluate lot-to-lot consistency of a new plant-derived quadrivalent virus like particle influenza vaccine in adults 18-49 years of age.

ABSTRACT

BACKGROUND: The global reliance on eggs to produce most influenza vaccines has several limitations and new approaches to influenza vaccine production are needed. Herein we describe a phase 3, lot-to-lot consistency trial (NCT03321968) of a quadrivalent, recombinant, virus-like particle (VLP) influenza vaccine produced in plants. This platform is based on transient expression of proteins in Nicotiana benthamiana and yields VLPs bearing hemagglutinin (HA) protein trimers that are combined in a quadrivalent vaccine (QVLP). METHODS: The HAs targeted in this study were A/California/07/2009 H1N1, A/Hong Kong/4801/2014 H3N2, B/Brisbane/60/08 and B/Phuket/3073/2013 recommended for the 2016-2017 Northern Hemisphere season. Healthy adults 18-49 years of age (n = 1200) were randomized 111 to receive a 0.5 mL intramuscular injection of QVLP (30 µg HA/strain) from three sequential lots. Local and systemic reactions were monitored for 21 days post-vaccination and blood was collected pre-vaccination and at day 21 (D21) after vaccination to measure hemagglutination inhibition (HI) antibodies. RESULTS: Subject demographics were similar between groups and compliance with study procedures was 96.3%. The study population was 54.8% female, the mean age (±SD) was 29.9 ± 9.01 and the racial distribution was 77.8% Caucasian, 15.6% Asian, 5.8% Black/African American and 0.8% other. The HI responses met the Center for Biologics Evaluation and Research criteria for seroconversion (SCR ≥ 40%) and seroprotection rates (SPR ≥ 70%). The geometric mean fold rise in HI titers was ≥ 2.5 for all 4 strains for each lot. Lot-to-lot consistency was met with the 95% confidence intervals of the D21 mean geometric titre ratios falling between 0.67 and 1.5 for all four strains. No safety concerns were identified. Solicited adverse events were generally mild and transient typical for what is reported after inactivated influenza vaccines. CONCLUSIONS: This study supported earlier findings of the safety profile and immunogenicity of the plant-derived QVLP and demonstrated the consistency with which it can be produced.