Written by: Sarah Wornow ‘23
Edited by: Geat Ramush ‘23
Receiving an influenza vaccine has become an annual tradition for most Americans. Especially important this year with the SARS-COV-2 pandemic coinciding with flu season, manufacturers have projected that they will produce 198 million doses of the flu vaccine, up from the record-setting 2019-2020 season where 175 million doses were prepared . How are all these vaccines produced? The answer, currently, is chicken eggs. Chicken eggs provide a suitable environment for an influenza virus to replicate. After being injected into the egg, the virus is incubated for a few days, then it is isolated, inactivated, and purified. This purified protein, the antigenic component of the virus, becomes incorporated into a vaccine.
This past flu season, 82% of all distributed influenza vaccines were egg-based. The two alternative methods to prepare an influenza vaccine currently include cell-based technologies, where the virus is grown in mammalian-derived cell cultures instead of chicken eggs, and recombinant technologies, where the virus is developed synthetically, also bypassing the use of chicken eggs . Both of these technologies are still relatively underdeveloped, and as such the majority of vaccines produced come from eggs.
Alternative technologies to egg-based vaccines are becoming more necessary, as there are three major problems that arise with the production of these vaccines. The first issue materializes when mutations occur in the influenza viruses grown inside these eggs. These mutations are called egg-adaptations, and they cause slight differences between the currently circulating viruses and the vaccine strain . These slight differences can cause a very low vaccine efficacy rate, as seen in the 40% efficacy rate of the 2012-2013 influenza virus . A second issue in using egg-based vaccines is the time needed to prepare enough doses for the general population. The CDC and other organizations around the world decide on the next season’s influenza virus at least 6 months in advance. This substantial time period ensures enough doses of the vaccine can be produced for the entire population because the replication process of the virus inside the egg takes a few days. Labs have limited capacity and limited supplies, so the vaccines have to be produced in batches over the span of a few months. Additionally, for every dose of the vaccine, one egg is used. Therefore, for the estimated 162 million egg vaccines that will be created for this year’s flu season, 162 million eggs are needed. The manufacturing time to mass-produce these vaccines depends heavily on the egg supply chain, which can be problematic. The last major issue with egg-based vaccines is that people with severe egg allergies are discouraged from getting one. There are currently only two licensed influenza vaccines that do not use eggs. New technologies are needed to combat these pertinent issues.
In late October, the results of the first phase 3 trial of a plant-based influenza vaccine were reported. The vaccine was shown to be effective and safe, paving the way forward for the continued development of this vaccine . Production of the vaccine, manufactured by Quebec-based biotechnology company Medicago, involves “infecting” a relative of the tobacco plant with a protein sequence from the influenza virus. The sequence incorporates itself into the plant’s genome, and the plant rapidly produces virus-like particles, or VLPs. VLPs contain no genetic information (meaning they can’t transmit disease), but instead they have an outer coat full of influenza surface proteins . As a result, VLPs can elicit a proper immune response without causing negative side effects. These VLPs are purified and utilized in a vaccine.
There are many advantages to using plant-based vaccines. Medicago predicts they would only need 5-6 weeks to mass-produce their vaccine due to the fact that it only takes one week to infect a plant and have it generate a substantial amount of VLPs . This reduced manufacturing time can enable a more accurate prediction of which influenza strains will be circulating during flu season, in turn increasing the efficacy of the vaccine. In addition, plant-based vaccines are much cheaper than egg-based vaccines and do not rely on the egg supply chain. Lastly, people who have severe egg allergies would be able to receive a plant-based vaccine.
Plant vaccines can potentially become the technology of choice for vaccine manufacturers in the future due to their versatility, cheaper cost, and decreased manufacturing time. Though still a long way away from becoming licensed and mass produced, these vaccines could provide a footprint for the rapid production of more accurate vaccines for a wide range of diseases, including SARS-COV-2.
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