The first pandemic of the 21st century—caused by the influenza A (H1N1) virus—underscored the need for the rapid and large-scale production of an effective vaccine. Traditional manufacturing methods, which rely on chicken eggs as a growth medium for the viral material in a vaccine, fell well short of this year’s global demand for the H1N1 vaccine. But a new production method could relegate such shortfalls to medical history.
Earlier this year, a team of Austrian scientists demonstrated that an H1N1 influenza vaccine could be created from virus-like particles (VLPs) that were derived from insect—moth—cells. Reingard Grabherr, of the University of Natural Resources and Applied Life Sciences in Vienna, and her colleagues showed that a pandemic influenza vaccine could be produced from VLPs within 10 weeks of isolating the RNA sequence of a new viral strain, which is much faster than the nine months typically required for a traditional influenza vaccine. The VLP-produced vaccines also provide predictable yields, so large batches can be made quickly. It’s a difference that could save millions of lives during a virulent influenza pandemic.
Unlike egg-produced vaccines, which contain inactivated virus particles, a VLP vaccine lacks viral genetic material. An H1N1 VLP consists of two key proteins from the influenza virus—hemagglutinin and matrix protein—and some of the lipid membrane from the insect cell. So VLPs are non-infectious and can’t replicate. “This makes their application in humans very safe,” says Grabherr. “VLPs can’t recombine with wild-type viruses or trigger the complications seen with traditional vaccines in immune-suppressed people.”
Despite the absence of genetic material, influenza VLPs are structurally similar to the pathogenic virus, and so generate a very effective immune response. In fact, VLPs trigger multiple immune pathways—the humoral immune response, which produces antibodies, and the cell-mediated response, which relies on specialized “killer” cells to rid the body of foreign particles. In contrast, traditional vaccines trigger only the humoral immune response. The activation of both pathways by VLPs creates a longer-lasting and stronger immune response.
An influenza VLP vaccine bypasses many other disadvantages of a traditional egg-produced vaccine, according to Grabherr, such as the “high risk of contamination, limited supply of pathogen-free eggs, and the potential for egg-protein allergies.”
The advantages of VLP vaccines have already been recognized by the pharmaceutical industry. For example, GlaxoSmithKline has marketed a vaccine—Cervarix, against the cancer-causing human papilloma virus—that is based on insect cell–derived VLPs.
Grabherr’s academic research group doesn’t have the capacity to produce a vaccine for clinical trials. Instead, she and her colleagues are currently working on ways to purify the influenza VLPs for use in an H1N1 vaccine. It might not be long before the world will be able to respond more quickly to an H1N1 pandemic. “I think that, realistically, with the implementation of our results, a product will be on the market within two to three years,” says Grabherr.