Getty | Felix Dlangamandla
The researchers have now reported data from early (and small) clinical trials of four candidate COVID-19 vaccines.
So far, the data is positive. The vaccines appear to be generally safe and stimulate immune responses against the new coronavirus, SARS-CoV-2. But whether these immune responses are sufficient to protect people from infection and disease remains an important question.
The four candidates are now headed for larger trials (phase III trials) that will test them: Can they protect people from COVID-19 and end this pandemic?
The challenge
While the first trials that looked at safety and immune response required dozens or hundreds of volunteers, researchers will now have to recruit tens of thousands. Ideally, volunteers will be in places that still have high levels of SARS-CoV-2 circulating. The more likely volunteers are to encounter the virus in their communities, the easier it will be to extrapolate if a vaccine is protective. As such, the researchers plan to do a significant amount of testing in the US and other parts of the Americas, which have largely failed to control the pandemic.
There has been a lot of debate about the use of “human challenge trials,” in which researchers would give young, healthy volunteers with low risk of COVID-19 an experimental vaccine and then intentionally expose them to SARS-CoV-2 in settings. controlled. This could potentially Provide a clearer and faster response on the efficacy of the vaccine. It is certainly an attractive idea given the catastrophic pandemic, and it is an idea that has gained traction in recent weeks. An advocacy group called 1Day Sooner has collected the names of more than 30,000 people willing to participate in such a trial, for example.
But experts remain divided on the idea. The main concern is that there is no “rescue” treatment for COVID-19 that can fully protect a test volunteer from serious illness and death if an experimental vaccine fails. Although young and healthy people have Less Risk that older people and those with underlying health conditions, some still suffer serious illness and death from COVID-19, and it is unclear why. Opponents also note that challenge trials may not be faster or necessary, given the high levels of spread of the disease in the U.S. and elsewhere.
Although the debate on challenge trials is ongoing, it is unclear whether researchers will end up needing or using them. Meanwhile, traditional Phase III tests are now underway, and have generated a lot of excitement from the public. According to a report this week, more than 138,600 people have signed up through the National Institutes of Health to participate in vaccine trials. If all goes well, we could have data from these trials by the end of the year.
So how do the top four vaccine candidates work and what do we know about them?
MRNA-1273: Modern, NIAID
MRNA-1273 is a messenger RNA (mRNA) vaccine made by the modern biotechnology company, which was working with the NIH National Institute of Allergy and Infectious Diseases (NIAID). The idea behind the mRNA vaccine platform is that it delivers fragments of the genetic code of a target virus, in this case, code in the form of mRNA, to human cells. Those cells can translate that code into viral protein. From there, the immune system can mount a response to the protein, which can be activated if the target virus ever tries to invade.
In the case of mRNA-1273, the researchers used a fat nanoparticle to package the mRNA encoding the SARS-CoV-2 spike protein, which is generally found protruding from the viral particles of SARS-CoV-2.
Vaccines that use genetic material (RNA or DNA) are new and have not been tested. As of yet, there are no approved vaccines that use this type of platform. It is unclear whether they will be successful here or elsewhere and, if they are, how easy it will be to manufacture such a vaccine on a global scale. (For information on different types of vaccine platforms, see our vaccination manual.)
On July 14, the researchers published results of a phase 1 trial, which primarily looks at safety in a small group of people. The study, which appeared in the New England Journal of Medicine, included 45 healthy volunteers between the ages of 18 and 55 and tested three dose levels of the vaccine. That is, there were three groups of 15 people, and each group received a low, medium, or high dose of the vaccine (25 microgram, 100 microgram, or 250 microgram dose). Each participant received two injections of their dose, 28 days apart.
Overall, the vaccine was found to be safe. More than half of the participants had mild to moderate side effects, primarily fatigue, chills, headache, myalgia, and injection site pain. Side effects were more common after the second dose, regardless of intensity, but those who received the two highest-dose vaccines reported more side effects. Two people (one in the 100 microgram group and the other in the 250 microgram group) had severe skin redness at the injection site. Two people in the 250 microgram group experienced lightheadedness and fainting.
All participants produced antibodies against SARS-CoV-2, with antibody levels increasing after the second injection. Those who received the highest doses had slightly higher levels of antibodies. The researchers compared the levels of participating antibodies with those seen in 41 people who had recovered from a COVID-19 infection. All the vaccinates had antibodies in the same range as the recovered people.
The researchers also specifically tested neutralizing antibodies – that is, antibodies that not only bind to a virus particle but can completely deactivate it. The researchers found that the vaccine caused higher levels of neutralizing antibodies than those seen in most of the people who recovered. For example, 57 days after the first dose, people in the 100 microgram group had neutralizing antibody titers ranging from 163 to 329, while the range was approximately 60 to 200 in patients who had recovered from COVID. -19.
Finally, the researchers looked at T-cell responses, which can attack virus-infected cells, and found that the vaccine generated certain types of T-cell responses to SARS-CoV-2.
In general, the results are encouraging but not conclusive. Researchers do not yet know what immune responses or antibody levels are necessary to prevent SARS-CoV-2 infection and / or disease. And, after just six months of the pandemic, it is unclear how long such protective immune responses would last.
According to a list in the NIH registry for clinical trials, Moderna plans to start a phase III trial of mRNA-1273 on July 27. Moderna wants to enroll 30,000 people in the trial, analyzing the efficacy and other safety and immune response data. .
AZD1222 (ChAdOx1 nCoV-19): University of Oxford, AstraZeneca
On July 20, the researchers published the results of a phase I / II trial of AZD1222, a candidate vaccine made by researchers at the University of Oxford and the international pharmaceutical company AstraZeneca.
AZD1222 (also called ChAdOx1 nCoV-19) is a vector-based viral vaccine. With this platform, researchers can group fragments of a dangerous virus into a much less dangerous virus. The mostly harmless viral packet is then delivered to the immune system, which can learn to search for and destroy the dangerous virus based on the contraband fragments.
In the case of AZD1222, the genetic material of the SARS-CoV-2 spike protein is packaged in a weakened type of adenovirus that infects chimpanzees. Adenoviruses that infect humans normally cause mild infections, often considered common colds. The chimpanzee virus, which generally does not infect humans, is made even more harmless by engineering that prevents it from replicating in human cells. In the first tests, AZD1222 protected the monkeys from the development of pneumonia after the researchers exposed them to high doses of SARS-CoV-2.
The results of clinical trials, published in The Lancet, show that AZD1222 is generally safe and stimulates immune responses in humans. The trial involved 1,077 participants (ages 18 to 55), 543 of whom were randomly assigned to receive AZD1222, and the remaining 534 received a meningococcal vaccine as a control. The researchers divided the participants into four groups and performed different types of tests on their immune responses. Ten of the participants who received AZD1222 were in a “booster” group that received a second vaccine after 28 days. The other participants who received AZD1222 received only one dose.
Mild AZD1222 side effects were common, including pain, fever, chills, muscle pain, headache, and general malaise. Some participants received paracetamol (acetaminophen / Tylenol) preventively to decrease these effects. No serious side effects were reported.
In 127 participants vaccinated with AZD1222, all produced antibodies against SARS-CoV-2. The levels were within the range observed in people who had recovered from COVID-19. The researchers conducted two separate tests to look for neutralizing antibodies in 35 vaccinated participants. In one test, 32 (91 percent) were positive for neutralizing antibodies 28 days after vaccination, and in the other test, 100 percent were positive. The ten participants who received a booster shot produced neutralizing antibodies, some of which were at higher levels than those typically seen in patients recovered with COVID-19. The researchers also reported that AZD1222 induced T-cell responses.
The researchers have already begun a phase III trial of AZD1222 at sites in Brazil, the United Kingdom, and South Africa. They also plan to test the vaccine in the United States soon. AstraZeneca said it will use two doses in the advancing trials to maximize immune responses.
