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

SPS commentary:

A related commentary describes the background to the research and the reasoning for investigating plant based influenza vaccines.  Circulating H3N2 viruses have become increasingly humanised (better adapted to infect human cells), which becomes an issue when the virus for the vaccine is grown in embryonated chicken eggs. During cultivation of the virus in eggs, it can adapt to attach better to the cell receptors on chicken cells, subtly shifting the sequence of the haemagglutinin antigen used for entry. Thus, the egg-derived haemagglutinin can be different to the haemagglutinin expressed by circulating H3N2 virus and antibodies raised against the vaccine strain are less able to neutralise the virus. Alternative manufacturing processes might circumvent problems of antigen mismatch caused by growth in eggs. Two alternative approaches have been licensed to date: using insect cells to make a recombinant protein and mammalian cell lines to grow virus. The effect of changing the influenza vaccine manufacturing platform on efficacy is variable. In one study, the recombinant-based vaccine was reported to have better efficacy than a cell-derived vaccine, but in another study no difference was seen. It concludes that this study 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.