Brian J Ward1, Annie Séguin2, Julie Couillard2, Sonia Trépanier2, Nathalie Landry3. 1. Medicago Inc., 1020 route de l'Église office 600, Québec, QC G1V 3V9, Canada; Research Institute of the McGill University Health Centre, 1001 Decarie Street, EM3-3248, Montreal, QC H4A 3J1, Canada. 2. Medicago Inc., 1020 route de l'Église office 600, Québec, QC G1V 3V9, Canada. 3. Medicago Inc., 1020 route de l'Église office 600, Québec, QC G1V 3V9, Canada. Electronic address: landryn@medicago.com.
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 1:1:1 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. Crown
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 1:1:1 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. Crown
Authors: Yao Ma; Ye Wang; Chunhong Dong; Gilbert X Gonzalez; Wandi Zhu; Joo Kim; Lai Wei; Sang-Moo Kang; Bao-Zhong Wang Journal: Small Date: 2022-05-23 Impact factor: 15.153
Authors: Maria Lobato Gómez; Xin Huang; Derry Alvarez; Wenshu He; Can Baysal; Changfu Zhu; Victoria Armario-Najera; Amaya Blanco Perera; Pedro Cerda Bennasser; Andera Saba-Mayoral; Guillermo Sobrino-Mengual; Ashwin Vargheese; Rita Abranches; Isabel Alexandra Abreu; Shanmugaraj Balamurugan; Ralph Bock; Johannes F Buyel; Nicolau B da Cunha; Henry Daniell; Roland Faller; André Folgado; Iyappan Gowtham; Suvi T Häkkinen; Shashi Kumar; Sathish Kumar Ramalingam; Cristiano Lacorte; George P Lomonossoff; Ines M Luís; Julian K-C Ma; Karen A McDonald; Andre Murad; Somen Nandi; Barry O'Keefe; Kirsi-Marja Oksman-Caldentey; Subramanian Parthiban; Mathew J Paul; Daniel Ponndorf; Elibio Rech; Julio C M Rodrigues; Stephanie Ruf; Stefan Schillberg; Jennifer Schwestka; Priya S Shah; Rahul Singh; Eva Stoger; Richard M Twyman; Inchakalody P Varghese; Giovanni R Vianna; Gina Webster; Ruud H P Wilbers; Teresa Capell; Paul Christou Journal: Plant Biotechnol J Date: 2021-07-19 Impact factor: 13.263