The quadrivalent, virus-like particle influenza vaccine has potential to offer substantial protection in adults.
The results from 2 phase 3 studies demonstrated safety and efficacy of a plant-derived influenza vaccine, thus making both studies the first large-scale trial of any such human vaccine.
Despite the public health threat that the seasonal influenza continues to pose, plant-based manufacturing has the potential to address some of the limitations of current vaccines, such as a potential mismatch between vaccine and circulating strains of influenza.
A team led by Brian Ward, MDCM, Medical Officer at Medicago, conducted the randomized, observer-blind, multinational studies in order to assess the efficacy of a plant-based recombinant quadrivalent virus-like particle (QVLP) influenza vaccine in adults 18-64 years and ≥65 years.
The 18-64 study included 10,160 participants across 73 sites. A smaller per-protocol population (n = 4814) was used to assess the vaccine efficacy while the entire population was included in the safety analysis.
The inclusion criteria were body-mass index <40 kg/m2 as well as good health.
Participants were assigned 1:1 to the QVLP vaccine (30 μg haemagglutinin per strain) or placebo.
The primary outcome sought by the investigators was 70% absolute vaccine efficacy, defined as preventing laboratory-confirmed, respiratory illness caused by antigenically matched influenza strains.
However, only 35.1% (95% CI, 17.9-48.7) absolutely efficacy was achieved for the QVLP population.
In terms of safety profile, 1.1% of those who received the vaccine experienced an adverse an adverse event—versus 1.0% in the placebo group.
Furthermore, 0.1% in both the vaccine and placebo groups had severe treatment-related treatment-emergent adverse events.
In the ≥65 years study, the investigators assessed a total of 12,794 participants across 104 sites, with a per-protocol population of 12,022.
Participants were randomly assigned 1:1 receive the QVLP vaccine (30 μg haemagglutinin per strain) or quadrivalent inactivated vaccine (15 μg haemagglutinin per strain).
The primary outcome for this study was relative vaccine efficacy to prevent laboratory-confirmed influenza-like illness caused by any influenza strain.
Thus, it achieved its primary non-inferiority endpoint with a relative vaccine efficacy of 8.8% (95% CI, -16.7 to 28.7).
The investigators reported that 4.1% of the vaccine-treated participants in the per-protocol subpopulation experienced serious adverse events. As for who received the quadrivalent inactivated vaccine, 4.2% experienced serious adverse events.
And finally, <0.1% of participants in both treatment cohorts had severe treatment-related treatment-emergent adverse events.
“Together, [the results of both trials] show that the plant-derived QVLP vaccine can provide substantial protection against respiratory illness and influenza-like illness caused by influenza viruses in adults,” Ward and team concluded. “QVLP vaccine was well tolerated and no major safety signal arose in participants who received QVLP vaccine across the two studies.”
In a separate commentary, John Tregoning, MA, PhD, Department of Infectious Disease, Imperial College London emphasized the importance and potential of alternative vaccine manufacturing processes.
“The field of plant-derived vaccines has grown a lot in the past 28 years, since it was first shown that viral proteins could be expressed in plants,” he wrote. “There is one licensed plant-derived human therapeutic for Gaucher's disease, but this is the first time a plant vaccine has been tested in a clinical trial. It is a milestone for this technology and sows the seeds for other plant-based vaccines and therapeutics.
He noted the drawback in speed at which plant material can be generated during a pandemic. However, he expressed an optimism that such limitations can be overcome, and thus gestured to Medicago’s phase 1 trial of a plant-derived coronavirus disease 2019 (COVID-19) vaccine.
The study, “Efficacy, immunogenicity, and safety of a plant-derived, quadrivalent, virus-like particle influenza vaccine in adults (18–64 years) and older adults (≥65 years): two multicentre, randomised phase 3 trials,” was published online in The Lancet.