Efficacy and Safety of a Recombinant Plant-Based Adjuvanted Covid-19 Vaccine

Abstract

Background Coronavirus-like particles (CoVLP) that are produced in plants and display the prefusion spike glycoprotein of the original strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are combined with an adjuvant (Adjuvant System 03 [AS03]) to form the candidate vaccine. Methods In this phase 3, multinational, randomized, placebo-controlled trial conducted at 85 centers, we assigned adults (≥18 years of age) in a 1:1 ratio to receive two intramuscular injections of the CoVLP+AS03 vaccine or placebo 21 days apart. The primary objective of the trial was to determine the efficacy of the CoVLP+AS03 vaccine in preventing symptomatic coronavirus disease 2019 (Covid-19) beginning at least 7 days after the second injection, with the analysis performed after the detection of at least 160 cases. Results A total of 24,141 volunteers participated in the trial; the median age of the participants was 29 years. Covid-19 was confirmed by polymerase-chain-reaction assay in 165 participants in the intention-to-treat population; all viral samples that could be sequenced contained variants of the original strain. Vaccine efficacy was 69.5% (95% confidence interval [CI], 56.7 to 78.8) against any symptomatic Covid-19 caused by five variants that were identified by sequencing. In a post hoc analysis, vaccine efficacy was 78.8% (95% CI, 55.8 to 90.8) against moderate-to-severe disease and 74.0% (95% CI, 62.1 to 82.5) among the participants who were seronegative at baseline. No severe cases of Covid-19 occurred in the vaccine group, in which the median viral load for breakthrough cases was lower than that in the placebo group by a factor of more than 100. Solicited adverse events were mostly mild or moderate and transient and were more frequent in the vaccine group than in the placebo group; local adverse events occurred in 92.3% and 45.5% of participants, respectively, and systemic adverse events in 87.3% and 65.0%. The incidence of unsolicited adverse events was similar in the two groups up to 21 days after each dose (22.7% and 20.4%) and from day 43 through day 201 (4.2% and 4.0%). Conclusions The CoVLP+AS03 vaccine was effective in preventing Covid-19 caused by a spectrum of variants, with efficacy ranging from 69.5% against symptomatic infection to 78.8% against moderate-to-severe disease. (Funded by Medicago; ClinicalTrials.gov number, NCT04636697 .)

Potential for a Plant-Made SARS-CoV-2 Neutralizing Monoclonal Antibody as a Synergetic Cocktail Component

“…However, the approval of ELELYSO by the FDA, along with the clinical development of ZMapp and 2G12, has cleared the regulatory pathway and slowly warmed up the interest of large pharmaceutical companies toward plant-made mAbs [ 66 , 67 , 68 , 69 ]. For example, Pfizer has entered into an agreement to license the worldwide rights for commercializing ELELYSO, and the very recent approval of a plant-made COVID-19 vaccine co-developed by Medicago and GlaxoSmithKline (GSK) [ 70 ] should facilitate the commercial development of plant-made mAbs and streamline the approval of those that have shown safety in human clinical trials.…”

Plant-Derived Human Vaccines: Recent Developments

“…Medicago Inc. subsequently followed up with a phase II/III trial to assess the immunogenicity, safety and efficacy of the CoVLP vaccine formulation and dosing regimen (NCT04636697). Most encouragingly, results show that the vaccine had 78.8% efficacy against moderate-to-severe disease and a 74% efficacy against seronegative participants [ 81 ]. Moreover, the vaccine elicited 69.5% efficacy against COVID-19 caused by five different variants including those of delta, gamma, alpha, lambda and mu.…”

“…However, over time, the consolidation of protocols, establishment of GMP-compliant plant production facilities, drafting of regulatory frameworks as well as techno-economic analyses [76][77][78] demonstrating feasibility and commercial applicability have established the production of vaccines in plants as a significantly more accepted enterprise [18]. A number have been tested in clinical trials [79][80][81] and the first plant-produced vaccine for human use against COVID-19 was recently authorised by Health Canada [20] after the successful outcome of phase III clinical trials [81]. Below, we discuss some of the more recent developments in the last 5 years (2018-2022) of plantproduced human vaccine research against various disease targets (Table 1).…”

Tunable control of insect pheromone biosynthesis inNicotiana benthamiana

“…N. benthamiana , a non-cultivated species native to Australia, has a comparatively shorter life cycle and does not accumulate large biomass in field conditions. However, it is particularly amenable to Agrobacterium -mediated transient expression (agroinfiltration), which has been exploited for the large-scale production of recombinant proteins including the production of coronavirus-like particles, approved as a COVID-19 vaccine in Canada (Chen et al, 2013; Hager et al, 2022; Stephenson et al, 2020). In recent years, this method has also been shown to be amenable for the reconstruction of many metabolic pathways, including the production of preparative quantities (van Herpen et al, 2010; Molina-Hidalgo et al, 2021; Reed et al, 2017; Stephenson et al, 2020).…”