Moderna has rolled our many versions of vaccines to fight against Covid-19 since the pandemic began in 2020. One of their latest versions of the Covid-19 vaccine is a streamlined version of its mRNA Covid-19 vaccine, called mRNA-1283. For those who don’t know, mRNA vaccines are vaccines that work by introducing a piece of mRNA that corresponds to a viral protein, usually a small piece of a protein found on the virus’s outer membrane. What is interesting about the mRNA-1283 vaccine and makes it seem quite efficient is that it is more effective at lower doses and lasts twice as long when stored in a refrigerator. This is likely due to a very unique feature of the mRNA-1283 vaccine: it does not include mRNA that corresponds to all parts of the famous SARS-CoV-2 spike protein—a protein on the SARS-CoV-2 virus that allows the virus to penetrate host cells and cause infection. Instead, it includes mRNA that corresponds to just two specific key parts of the spike protein.
Many studies have shown that the most effective antibodies to fight against Covid-19 are those that bind to one of the two key sites of the spike protein that protrude from the virus’s surface. For instance, one of these two key sites is the region on the spike protein responsible for attaching to human cells and assisting the virus in entering the human cell. Therefore, antibodies that bind to this key site will block the spike protein from attaching to the human cell and entering the cell.
A majority of the current existing Covid-19 vaccines, including other existing Moderna vaccines, contains the entire spike protein. This causes the immune system to create antibodies against all parts of the spike protein, meaning that many of these antibodies are ineffective because not all parts of the spike protein are responsible for entering or harming human cells. On the other hand, Moderna’s mRNA-1283 vaccine consists only of mRNA coding for the two parts of the protein that contain the two key sites of the spike protein that are harmful to human cells, which means all of these antibodies are effective.
When the the first human trial of mRNA-1283 was given, it revealed that even when people were given a tenth of the full dose for one of Moderna’s original Covid-19 vaccines, called mRNA-1273, they produced an antibody response that was just as strong as a full dose of this original mRNA-1273 vaccine, according to a trial released in October 2022.
Additionally, the mRNAs in the mRNA-1283 vaccine are shorter than those in the mRNA vaccines coding for the entire spike protein, reducing the chance of mRNA breakdown and allowing the vaccine to last longer. When stored at temperatures between 2 and 8 degrees Celsius, the mRNA-1283 vaccine takes a year for 40 percent of the mRNAs to degrade, while the mRNAs in mRNA-1273 take only six months to degrade at these temperatures.
This connects to what we have learned in AP Bio class as in AP Bio we learned about the process of adaptive immunity. We learned that an adaptive immune response occurs when all the first and second line defenses of the body, such as skin or mucus, are unsuccessful in preventing a virus, such as Covid-19, or bacteria from spreading in the body. An adaptive immune response is then needed to target the virus or bacteria. Adaptive immune responses rely on two types of lymphocytes: B cells and T cells. B cells are the cells that take on the invading Pathogen, so in the case they would take on the SARS-CoV-2 in the body directly, while the T cells target the cells that were already infected by the virus. The adaptive immune response begins when the Macrophage cells of the body engulf the antigen through phagocytosis and then the vesicle formed for the antigen once engulfed inside the Macrophage fuses with a lysosome to break down the antigen. As the lysosome breaks down the antigen, it preserves the foreign antigen (epitope) which is the little part of the antigen that is recognized by the immune system. The epitope is then displayed on the outside of the macrophage membrane on the MHC protein. The T-helper cells see this displayed foreign antigen on the MHC protein and use their receptors to identify and recognize this foreign antigen. Once the T-helper Cell recognizes these proteins, it is now activated and releases interleukin which signals the start of the process to fight the foreign invader (the key sites on the spike protein) and activates the B and T cells. In the Humoral Response, the B cells bind to the foreign antigen that the T-helper cell recognized and once recognized by the B-cell, the T-helper cells help create the B-plasma cells. These B-plasma cells create antibodies to bind to and neutralize the foreign antigen.
In the case of covid-19, the foreign antigen, or small piece of the antigen that is recognized by the immune system, are the two key sites on the spike protein that we discussed. The T-cells recognize these key sites when they are embedded on the MHC protein and activate which releases interleukin and signals the start to the immune response. One of these immune responses is the Humoral Response which activates the B-cells to bind and recognize these key sites on the spike proteins as well. From here, the T-helper cells help create the B-plasma cells which create antibodies to surround and neutralize the two key parts of the spike protein (the foreign invader). Antibodies produced by covid-19 vaccines that are for the whole spike protein are producing some antibodies that are not going to surround and attack these two specific key sites of the spike protein/ the foreign antigen. On the other hand, the mRNA-1283 vaccine only produces antibodies that attack the specific key sites on the spike proteins (the foreign invader), so it is not producing any antibodies that are ineffective in fighting SARS-CoV-2. This makes the mRNA-1283 vaccine just as effective or more effective in smaller doses as other vaccines that produce antibodies for the whole spike protein are in larger doses because even though the vaccines for the whole spike protein are producing more antibodies, some of these antibodies don’t fight the specific foreign antigen that is preserved when the antigen is broken down by the lysosome in the Macrophage cell and needs an immune response, and instead try to fight the whole antigen (the whole spike protein) which is unnecessary.
As Covid-19 continues to evolve, more and more versions of Covid-19 vaccines are emerging, making it increasingly challenging for people like myself to decide which vaccine is truly ‘the best’ and should be taken. After delving deeper into the Moderna mRNA-1283 vaccine, it seems that, due to its exclusive focus on the key aspects of the SARS-CoV-2 spike protein, this version of the Covid-19 vaccine could indeed be at the top of the list for the most efficient Covid-19 vaccines. As someone who has fallen ill after receiving a Covid-19 vaccine in the past, the prospect of receiving a lower dosage of the Covid vaccine while still achieving the same or better effectiveness is definitely intriguing to me. When it is time for you to get your next Covid-19 vaccine, would you be interested in trying Moderna’s mRNA-1283 vaccine as your next Covid vaccination?