Immunogenicity and safety of a quadrivalent plant-derived virus like particle influenza vaccine candidate—Two randomized Phase II clinical trials in 18 to 49 and ≥50 years old adults

Abstract

Background New influenza vaccines eliciting more effective protection are needed, particularly for the elderly who paid a large and disproportional toll of hospitalization and dead during seasonal influenza epidemics. Low (≤15 μg/strain) doses of a new plant-derived virus-like-particle (VLP) vaccine candidate have been shown to induce humoral and cellular responses against both homologous and heterologous strains in healthy adults 18–64 years of age. The two clinical trials reported here addressed the safety and immunogenicity of higher doses (≥15 μg/strain) of quadrivalent VLP candidate vaccine on 18–49 years old and ≥50 years old subjects. We also investigated the impact of alum on the immunogenicity induced by lower doses of the vaccine candidate. Method In the first Phase II trial reported here (NCT02233816), 18–49 year old subjects received 15, 30 or 60 μg/strain of a hemagglutinin-bearing quadrivalent virus-like particle (QVLP) vaccine or placebo. In the second trial (NCT02236052), ≥50 years old subjects received QVLP as above or placebo with additional groups receiving 7.5 or 15 μg/strain with alum. Along with safety recording, the humoral and cell-mediated immune responses were analyzed. Results Local and systemic side-effects were similar to those reported previously. The QVLP vaccine induced significant homologous and heterologous antibody responses at the two higher doses, the addition of alum having little-to-no effect. Serologic outcomes tended to be lower in ≥50 years old subjects previously vaccinated. The candidate vaccine also consistently elicited both homologous and heterologous antigen-specific CD4 + T cells characterized by their production of interferon-gamma (IFN-γ), interleukine-2 (IL-2) and/or tumor-necrosis factor alpha (TNF-α) upon ex vivo antigenic restimulation. Conclusion Overall, the 30 μg dose produced the most consistent humoral and cellular responses in both 18–49 and ≥50 years old subjects, strongly supporting the clinical development of this candidate vaccine. That particular dose was chosen to test in the ongoing Phase III clinical trial.

High Level Production of Monoclonal Antibodies Using an Optimized Plant Expression System

“…The advances in the field of plant-made antibodies can be clearly seen by the first in-human clinical trial of the anti-cancer antibody 2G12 made in transgenic tobacco plants (Ma et al, 2015). Recently, a plant-made quadrivalent influenza VLP vaccine showed sustained, strong cross-reactive immune responses and has advanced to phase 3 clinical trials (Pillet et al, 2016(Pillet et al, , 2019.…”

What Does Plant-Based Vaccine Technology Offer to the Fight against COVID-19?

“…Additionally, production of IFN-γ, IL-2, and/or TNF-α was achieved upon ex vivo antigenic re-stimulation. [46] Vaccines 2020, 8, 183 7 of 19 Table 2. Cont.…”

Will plant-made biopharmaceuticals play a role in the fight against COVID-19?

“…At least one product has entered the market, namely taliglucerase alfa, a carrot-made enzyme obtained in bioreactors that is prescribed as replacement therapy for Gaucher´s disease [10]. Other products are close to be approved, for instance, clinical trials are ongoing to evaluate influenza vaccines produced by Medicago Inc [13]. Moreover, Zmapp (a plant-made monoclonal antibody cocktail) was placed in the spotlight during the Ebola outbreak in 2014 since it was administered to two patients on a compassionate basis to treat a few patients [14].…”