Enlarge /. Test doses of another potential SARS-CoV-2 vaccine.
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We still don't know how well a robust immune response protects people from SARS-CoV-2 infection. However, we have another indication that vaccines can trigger a strong immune response. Shortly before the holiday weekend, a Chinese team published the results of a security experiment with a harmless virus that was modified to carry one of the coronavirus genes. Although there were a number of side effects, everyone who received the vaccine showed a robust antibody response, including some antibodies that neutralized the virus.
Known virus, new protein
The first indication of progress toward a vaccine that we know of was a company press release. This new article is published in the form of a peer-reviewed article in the renowned medical journal The Lancet. Most of its authors are academic researchers or health authorities; Only two are associated with one company.
The two reports also differ significantly in their approach to generating an immune response. The earlier announcement by a company called Moderna involved injecting carefully packaged RNAs that code for the spike protein that is normally found on the surface of the virus. The RNAs migrate into a person's cells, causing them to produce the spike protein, exposing the immune system to it.
The Chinese researchers took a completely different approach to inducing immunity. In their case, they developed the gene encoding the spike protein into a harmless virus called adenovirus 5. They then produced large amounts of the manipulated virus and injected it into humans. Although adenoviruses are essentially unrelated to coronaviruses (using DNA as the genetic material instead of RNA), the cells that infect the engineered viruses produce the coronavirus spike protein, which exposes the immune system to it again.
However, the adenovirus is not without complications, especially because many of us have had it before. In that case, this may not be a bad thing. The primary side effects are mostly what you would expect from injections of a virus: injection site inflammation, as well as fever, fatigue, and muscle aches that are typical of a viral infection. Most of these occurred in just under half of the 108 participants, of whom over 80 percent experienced at least one. But those who had high levels of antibodies to adenovirus 5 tended to have fewer side effects.
None of the side effects were classified as serious and all participants stayed with the study during the 28-day study. However, it was potentially problematic to find that a strong adenovirus 5 immune memory slightly reduced the immune system's response to the spike protein.
The researchers followed a sensitive test to determine whether injections of the vaccine induced the production of antibodies. Antibodies to the coronavirus spike protein were seen 14 days after the vaccine was injected. After 28 days, all but three of the 108 participants had a sharp increase in the antibody level against the spike protein. When quantifying the changes, the researchers found that a high dose of the vaccine injection elicited a response that was more than twice that of the low dose group, with the mean dose in between. There was also a T cell response to the spike protein, which is important for a strong overall immune response.
The researchers also looked for antibodies that neutralized SARS-CoV-2 and prevented it from infecting additional cells in culture. These were present in all groups tested, and their frequency increased with the vaccine dose.
Overall, this is good news. But it is also incomplete. The neutralization of a virus in culture is very different from the neutralization in an actual organism. In the past, there have been cases where a vaccine has induced antibodies that make it easier for a virus to infect cells (by stabilizing the conformation in which the virus attaches to cells). So we do not know whether the antibody production shown here means protection – this is a problem for the next round of experiments.
The authors also find that their participants were all under the age of 60, so the population with the highest risk of infection was not taken into account.
However, the work follows a number of similar studies that indicate that it is not difficult to generate an antibody response to SARS-CoV-2, and this response typically includes antibodies that neutralize the virus in tests. What we currently lack is two important pieces of information. One is whether neutralizing antibodies effectively block the spread of the virus in humans. We should get some information about it when we start completing attempts to use blood plasma from previously infected people.
The other key question now is that every immunity lasts a long time. There have been some reports of possible new infections, but they remain rare and the details of what happens are missing. This can be a question that we only need time to answer.
If you would like details about the design of the study, you can download it from ClinicalTrials.gov.
The Lancet, 2020. DOI: 10.1016 / S0140-6736 (20) 31208-3 (Via DOIs).