The modern biotechnology company, one of the many organizations developing a vaccine for COVID-19, published results of an early-stage test of his experimental mRNA vaccine in the New England Journal of Medicine July 14. Sanjay Mishra, a staff scientist at Vanderbilt University Medical Center and an expert in protein chemistry, explains the meaning of the results of phase 1 of the trial.
What was Moderna testing for?
They tried two things: proof of concept and if there are any side effects.
What was the results?
The results just published in the New England Journal of Medicine are provisional. We have to be very clear about it.
This particular batch of results is 45 adults between the ages of 18 and 55 who were not screened for infections. [for COVID-19]. We would then call them healthy adults, although no serology or PCR (polymerase chain reaction) tests were performed before the trial began.
They were given one of three doses: 25, 100, or 250 micrograms. More than half of the participants had discomfort, such as fatigue, chills, headaches, myalgia (muscle pain), and pain at the injection site. After 28 days, exactly the same dose was administered a second time. After the second dose, these discomfort events were much more common. But overall, it can be said that nothing serious was reported. And then on the 29th, blood was drawn.
These blood samples were analyzed for their antibody response. They found that antibody responses, unsurprisingly, were highest with the highest dose. They were slightly higher than would be expected in patients who had been recovering from a coronavirus infection.
They tested these things in three different ways. One of these is where you are testing the amount of antibodies produced. They then also tested the efficacy of these antibodies in serum using two different methods. All in all, there seems to be a binding and neutralization of the virus.
But the second batch of results, which comes from older patients, has yet to be announced. So that would come further down the line. After that, they hope to get the third batch of results, which will include the durability of immunity for both age groups in a single batch.
[[[[You must understand the coronavirus pandemic and we can help you. Read the The Conversation newsletter.]What conclusions can we draw?
The results are promising. At least they demonstrated the concept. The results show that when this vaccine is administered, the body produces antibodies. But we don’t know if those antibodies will lead to immunity in the body because all the results we have are seen outside the body [in blood samples].
And for the test to come from a larger data set in the next stage. So we would know if the people who received these vaccines are at least 50% less likely to get infected [to meet FDA guidelines for vaccine efficacy]. So they are good results, they are promising results, but they are quite early in the game, so to speak.
Can you explain what the company’s mRNA vaccine is and why it is different?
Vaccines are intended to train the immune system to attack the virus that causes the disease. In the case of SARS-CoV-2, there is a spike protein, or protein S, which is the flag that the immune system needs to recognize as the virus signature. Therefore, the goal of a vaccine is to train your immune system to recognize protein S and then trigger the immune response. This S protein is the standard in all coronaviruses, which is why they are called coronaviruses, because the “crown” is the crown.
Traditionally, vaccines involved a weakened virus or a virus preparation that would have contained (in this case) the spike protein. In the cleaner method, he would have produced the spike protein in the laboratory and then used it as a candidate for immunization.
All of these methods are time consuming and require extensive quality control. And there is usually a lot of headache when scaling from lab to production. The Moderna vaccine and another candidate vaccine bypass this process by using mRNA or messenger RNA. It is a genetic coding material that will help your body make that protein. In this way, you do not have to deal with the production of the protein in the laboratory and you run the risk of creating an impure protein sample, which can be clinically difficult to standardize and can also be dangerous.
So in this case, what you’re giving is not the protein or part of the virus, but a synthetic messenger RNA in a lipid drop.
How did you feel when you heard the news?
I am cautiously optimistic. The study provides promising data on safety and immunogenicity, or the ability to elicit an immune response. It is a good starting point to train the body’s immunity. But if I can paraphrase Robert Frost, we still have miles to go before bed.
Vaccine development is complex and there is much more work to be done before this can become a real marketable candidate.
This first batch of data is from the 18-55 age group. We do not know what the dose would be for the older age group, which is the most vulnerable to COVID-19. As we age, we don’t produce as many antibodies, which generally leads to a poor vaccine response. So the question is: Will they have to opt for a higher dose, which is usually the case in flu vaccines? The higher dose, which is 250 micrograms, has caused somewhat more serious side effects in this study. So how would that balance? It is still difficult to say.
What other vaccines are being developed?
There are 178 COVID-19 vaccines in various stages of development, and 14 are leading to human trials, including AstraZeneca and others. There are more potential candidates from Merck, Johnson & Johnson and others. There is a similar vaccine that is already being tested by Pfizer and BioNTech, and which has also shown positive results at the lowest doses.
This article is republished from The Conversation, a non-profit news site dedicated to sharing insights from academic experts.
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Sanjay Mishra does not work, consult, own shares or receive funds from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond his academic appointment.
