Russia is one of the countries most affected by the COVID-19 epidemic. But his response has been a bit … unusual. Like many other countries, Russia worked to develop its own vaccine. But while that development was still in progress, it announced that it would not wait for detailed safety data, instead of turning the vaccine into millions. Shortly afterwards, it became clear that a standard Phase 3 clinical trial would indeed be conducted in the country, albeit a large case involving 40,000 people.
It was difficult to determine whether any of these were justified, as few details about the vaccine itself were available. But on Friday that changed somewhat, as vaccine developers released results from initial clinical trials. And so far, it seems as effective as some of the other candidates for the vaccine, which has made it past the initial tests.
Are two viruses better than one?
According to our previous coverage, the vaccine is made up of two different engineered viruses. This involves the backbone of an innocent virus, called an adenovirus, which is engineered to contain a gene that encodes the main surface protein from the SARS-CoV-2 virus. This protein, called a spike, acts to lure and insert coronavirus cells. The use of adenovirus allows the immune system to learn to recognize spike proteins when the body only experiences a harmful adenovirus infection.
The point of this approach is that many people have already been exposed to the adenovirus, and so it can mount a strong immune response to it. This can lead to side effects that seem like the body’s normal response to a viral infection. (This was seen in trials of adenovirus-based vaccines developed in China.) But it can also limit the immune response to spike proteins, as the immune system focuses on parts of the engineered virus that are familiar.
To test the vaccine, the researchers enrolled two groups of 38 people. The first group received a single injection of engineered adenovirus to produce spike protein. The second group received the same initial injection, but was followed by a booster using a different strain of engineered adenovirus from the spike.
The idea behind using two differently engineered viruses is that, even if the immune system reacts to the adenovirus used in the first injection, it will not try to attack the one used in the booster. Ideally, it should acquire immunity to focus on one thing in common between these two viruses: the spike protein.
Side effects and antibodies
As expected, with or without a booster, many of those who were vaccinated had side effects that you are likely to get from a viral infection. These include fever, headache, general weakness and muscle and joint pain. Other than that, only one side effect was noted which was pain at the injection site. None of these were rated as serious, and all participants in the vaccine-plus-booster group were able to go on the booster.
Among those who received a shot, about 85 percent developed SARS-Co-2 specific antibodies two weeks later. After three weeks, each had antibodies against the virus. The same number was observed in the shot-plus-booster group, although the booster increased the levels of antibodies.
The researchers also discovered the presence of neutralizing antibodies, which bind the spike protein in a way that prevents it from contacting and / or entering cells. These antibodies are often considered essential for protection against viral infections, although the degree to which they are true for SARS-Cavi-2 has not yet been determined. Here, the use of booster injections made a big difference. Without it, less than one-third of participants neutralize antibodies. With Booster, everyone did.
Another potential advantage of using a virus to deliver spike proteins is that it incorporates all the common features of the immune response – antibody-producing B cells and T cells that identify infected cells. The researchers confirmed that vaccination activates T cell responses in participants, which may lead to stronger immunity. And they found that many of these T cells reacted to spike proteins instead of adenoviruses.
Works on ice
One of the nice results reported here is that, despite the need for an intact virus to work, the vaccine worked after it was stabilized (although its effectiveness was not comparable to a stable vaccine). In fact, the researchers were able to generate an immune response that was slightly reduced using a dry frozen vaccine and then dissolved again in water. Researchers have suggested that most of the vaccine will be given from frozen stocks, but the freeze-dry version will be used for communities that are not very accessible, of which Russia is the number one.
Overall, this is what you want to see before moving on to larger tests – there are no major side effects associated with building an immune response in which antibodies are neutralized. But big tests will be necessary for some reason. One is that we need to know if there are rare but serious side effects, which can only be evident in a large population. And the second is that we need to know that the neutralization of antibodies is really protective that something can be established by vaccinating a sufficient population that some will inevitably come in contact with SARS-CoV-2.
This is not the only adenovirus-based vaccine that is in development, and many of them are already moving into large-scale testing. If one succeeds, it probably means good news for others who have not yet. And if not, we’ll have to wait for one of the other techniques to make it a trial.
Lancet, 2020. DOI: 10.1016 / S0140-6736 (20) 31866-3 (About DOI).
