COVID-19 – Are We Nearing the Endgame?

I suspect that everyone has heard the highly encouraging news this week from two vaccine manufacturers, Pfizer/BioNTech and Moderna. Both companies released the first phase 3 trial preliminary results this week and based on these early data each of their vaccines is highly effective after 2 doses. In the case of Pfizer’s vaccine, the initial report was 90% efficacy, but this was quickly followed by an update indicating 95% efficacy. While the overall numbers are still small, the data to date show similar efficacy rates across races and ethnicities. Significantly, the efficacy in the vulnerable group of people over 65 years of age was still 94%. This is outstanding for an age group that often responds less reliably to vaccinations due to age-related declines in the overall immune response. Additionally, there was only 1 severe case of COVID-19 in the vaccinated group compared to 9 cases in the control group, suggesting that the vaccine reduces serious disease even in individuals that it doesn’t fully protect. Similar results were reported for the Moderna vaccine with a 94.5% overall efficacy rate and no severe COVID cases in the vaccinated group compared to 11 severe cases in the control group. No major side effects arose for either vaccine, although some individuals did develop short-lived fevers, fatigue, headaches, muscle/joint pain, or swelling with pain at the injection site, all similar to the common side effects seen with many other vaccines. Both companies have applied for emergency use authorization so that vaccine distribution and administration can begin as quickly as possible.

With these two vaccines about to be released for public use, you may be wondering what is in these vaccines and how they work. Traditional viral vaccines inject whole viruses or purified viral surface proteins. When whole viruses are used in the vaccine they are either live, weakened forms of the virus (called attenuated vaccines – for example, the chickenpox vaccine) or inactivated vaccines (such as the influenza vaccine) that are “killed” versions that have been chemically treated so that they are no longer infectious. For both the live and inactivated viral vaccines, the injected viruses retain their authentic shape and present their normal surface proteins to our immune system which responds by producing neutralizing antibodies. If you are later exposed to the authentic virus, the neutralizing antibodies will coat the virus and prevent it from entering your cells so it is unable to establish an infection. While they are generally safe and effective, there are disadvantages to using whole virus vaccines. Not only is there some chance for significant side effects in certain individuals, but they are also difficult to manufacture and require stringent quality control to ensure that no pathogenic virus is present in the final vaccine batches. As an alternative, protein-based vaccines have been developed for some viruses such as the Hepatitis B vaccine and human papillomavirus vaccine. For these vaccines, only a purified viral surface protein is present in the vaccine to elicit the anti-viral neutralizing antibodies. For these protein vaccines, there is no virus present in the vaccine and nothing that can cause the target disease so they are quite safe. Still, producing and purifying proteins is technically challenging so other methods have been pursued, including the new technology for both the Pfizer and Moderna vaccines that use messenger RNA (mRNA) as the active ingredient.

mRNA is the molecule used by the cells to produce proteins. DNA contains the genes that specify proteins, but to make the proteins, the DNA information is first copied into mRNA. The mRNA then is “read” by a cellular “machine” called the ribosome that converts the mRNA information into amino acids and links the amino acids together to form the protein chain. For the new COVID vaccines, mRNA that encodes the SARS-CoV-2 spike protein is the primary component of the vaccine. When these mRNA vaccines are injected, the mRNA enters our cells and is converted to the viral spike protein by our own ribosomes. This newly made spike protein in our cells is recognized as foreign by our immune system which responds by producing neutralizing antibodies against the spike protein.  These neutralizing antibodies will protect us against the SARS-CoV-2 virus if we are ever exposed. The advantage of mRNA vaccines compared to proteins is that mRNAs are much easier to produce and manufacture while being just as safe since again there is no virus in this type of vaccine to cause disease. A second important feature of mRNA for vaccines is that mRNA is very unstable and easily degraded. After producing spike protein for a short time in the cells the vaccine mRNA will degrade so that no trace of the vaccine material remains behind to cause any long-term problems. To protect the mRNA from degradation during storage and delivery to the cells the mRNA is packaged inside lipid nanoparticles (proprietary formulations by each company) that also facilitate mRNA uptake by the cells. Even with this lipid protection, both the Pfizer and Moderna vaccines require storage well below freezing to maintain the mRNA integrity, with the Pfizer vaccine needing extreme cold (-100 degrees Fahrenheit). Fortunately, cold storage isn’t a deal-breaker, especially when the disease danger is high and the vaccine efficacy is outstanding. Hopefully, these two vaccines, along with others in the development pipeline, will quickly squelch this raging pandemic.

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