Vaccines based on the Spike protein provide protection against COVID-19. Image shows viral particle with the S protein in red in the center. On each side is the 3-D structure of this protein complex showing each S protein in the complex in a different color. [Compilation by Nancy R. Gough, BioSerendipity, LLC
Vaccines that Work Provide Hope for an End to the Pandemic
Clinical trial results from 3 vaccines show that the vaccines have good efficacy. This means that they protect the people who receive the vaccine from getting severe COVID-19. Two of the vaccines are based a new technology that has not been used before in approved vaccines. The technology is new, however, it is not completely different from some other vaccine technologies. The two vaccines deliver instructions (in the form of nucleic acid) for your own cells to make a protein that the virus makes, so your body will recognize when the virus is present and prevent it from infecting your cells. Other approved vaccine technologies do the same thing, they just provide the instructions in a different form and deliver it to your cells in a different kind of “package” (Figure 1).
Pfizer and BioNTech collaborated on an mRNA-based vaccine that was 95% effective at preventing COVID-19 according to their press release. This protection was observed beginning 28 days after the first dose. The vaccine required 2 doses to work though. The clinical trial had more than 43,000 people, and there were 170 cases of COVID-19. Of those 170 cases, only 8 were in the group that had received the vaccine. All of the other 162 cases were in the group that received the placebo. Another important piece of data was that there were 10 severe cases of COVID-19 with 9 happening in the placebo group. Additionally, the vaccine was 94% effective in adults over 65 years old, which is particularly important. This population is one of the most at risk for developing severe COVID-19. All of this information is from a press release, so the results have not be published and peer reviewed. However, the results are so encouraging that the companies have applied for emergency use authorization from the FDA.
This vaccine, which is called BNT162b2, requires 2 doses to achieve the reported efficacy. An important consideration for delivery of this vaccine to the public is that the vaccine must be stored and transported at an extremely low temperature, -70°C (-94°F). So, this is good news but not “save the world” news, because of the storage and transportation requirements. However, the logistics of delivering such a cold-requiring vaccine are being addressed.
Moderna also developed an mRNA-based vaccine and reported that their vaccine was 94% effective. These results of the clinical trial were based on 95 cases of COVID-19 and the trial included more than 30,000 participants. Five of the 95 cases were in the group that received the vaccine. All 11 cases of severe COVID-19 were in the placebo group. Like the Pfizer and BioNTech vaccine results, these results are from a press release. However, these results are positive enough that the European Medicines Agency is performing a review of this vaccine as part of the next step to vaccine approval in Europe, and Moderna intends to apply for emergency use authorization in the US.
Like the BNT162b2 vaccine, this vaccine by Moderna, which is called mRNA-1273, requires 2 doses to achieve the reported efficacy. Compared to the Pfizer and BioNTech vaccine, the Moderna vaccine requires a higher dose. On the plus side though, this vaccine is stable at -20°C (-4°F) for up to six months, at refrigerated conditions for up to 30 days, and at room temperature for up to 12 hours. This is closer to “save the world” news.
Both the Pfizer/BioNTech and Moderna vaccines deliver mRNA, a type of instructions that cells use to produce proteins. The mRNA is engineered for maximum stability and delivered inside a nanoparticle composed of lipids or fatty like molecules that are similar to the molecules that make up the membrane surrounding our cells. Nanoparticles are like tiny biologically based soap bubbles. The nanoparticles prevent the mRNA, which is highly unstable, from being degraded, and help the vaccine get into cells. Using the mRNA molecules, cells injected with the vaccine or that take up the vaccine make a protein from the SARS-CoV-2 virus called Spike or S. The S protein binds to receptors on the surface of our cells and is how the virus enters our cells causing infection.
AstraZeneca and the University of Oxford, UK, also reported positive results with a SARS-CoV-2 vaccine. Like the other vaccines, this vaccine also provides cells instructions for making the S protein from SARS-CoV-2. This vaccine uses DNA as the instructions and the DNA is packaged inside an engineered virus called chimpanzee adenovirus. This adenovirus cannot replicate or cause infection itself; instead, is serves as the delivery system for the DNA molecule that has the instructions for making S. An advantage to this type of vaccine is that it is more stable than an mRNA vaccine delivered inside a lipid nanoparticle (Figure 1).
AstraZeneca reported results from a study with 23,000 participants who were in one of the following groups: One smaller group received 2 doses of a half dose followed by a full dose, a second received 2 doses of the full-dose amount, and the last received a vaccine against a different pathogen followed by an injection of saline. The different dosing regimens had different efficacies: The half dose followed by a full dose had 90% efficacy and the full dose followed by another full dose had 62% efficacy. Although it is not really appropriate to average these results, many news reports have stated the average of 70%. Given that the half-dose/full-dose regimen had a better effect and that less material would be required, it seems unlikely that AstraZeneca would proceed with the 2 full-dose regimen. However, only 2,741 subjects in the trial received that dose, which was a “mistake” according to AstraZeneca Executive Vice President Mene Pangalos, Ph.D.
This mistake is serendipitous. If it turns out that this dosing regimen works for most populations — old, young, and people with comorbidities — it could mean that less vaccine is needed and can immunize more people than the number that could be immunized with the full 2 dose regimen. However, additional trial data are needed with more subjects to know if there half dose/full dose regimen is best for everyone. If that dosing regimen only included young college students, then the test population is not representative of all groups. It is entirely possible that different groups, like older people, will respond differently and benefit more from the higher dosing regimen.
All 3 of these vaccines that have demonstrated efficacy in clinical trials provide instructions for cells to make the viral S protein (Figure 2). S protein was selected for vaccine development, because an immune response mounted against the S protein has a high chance of generating immunity that prevents infection. This hypothesis seems true based on the results of these clinical trials.
Among the things we do not know yet are if either of these 3 vaccines prevent asymptomatic disease or spread of the virus. We also do not know how long immunity will last. What we do know is that there are vaccines that protect people from getting severe COVID-19. With combinations of various vaccines, we will reach “save the world” news and end this pandemic.