Three vaccines show their effectiveness – ten open questions about them

A Russian vaccine was approved in the summer before being tested in classic efficacy studies. These tests are still ongoing.

Andrey Rudakov / Bloomberg

Press releases with the first interim results on the efficacy of Covid-19 vaccines are currently published weekly. The latest comes from the University of Oxford, which is developing a vaccine with AstraZeneca. As a result, the active ingredient prevents the disease in 70 percent of vaccinated people. Biontech / Pfizer and Moderna had previously shown better results. Biontech reported 90 percent effectiveness on November 9. After a second analysis, which included more data, the value was as much as 95 percent. The publication of Moderna is also good. According to this, 94% of infections should be prevented by the vaccine. This is full of hope. Whether vaccines will prove truly viable, however, still depends on many unknowns. Here we have put together ten important questions that will also be important when comparing different candidates.

So far, the companies have only published the results in the form of press releases. Since a lot of information is missing, it is not very significant. Proper evaluation of vaccines will not be possible until the data appears in a scientific publication. Biontech / Pfizer and Moderna use vaccines based on the mRNA method. The University of Oxford and AstraZeneca rely on a genetic ferry. Genetic information from coronaviruses is introduced into the human body by a weakened adenovirus. Both methods cause the body’s cells to make a protein from the virus. This is recognized by the immune system as a foreign body, so that a defense is prepared.

The University of Oxford achieved different results in two different approaches: a 90% efficacy in a group of 2,741 subjects in the UK and a protection of 62% in a study arm in Brazil with 8,895 subjects. All in all, it was 70 percent. A total of 131 people were infected with the virus in the study. In Brazil, test subjects were given the same dose twice with an interval of one month. Test subjects in Great Britain, on the other hand, received half a dose first and the full dose with the second vaccination only. It is not yet clear whether the dosage explains the different results or if there are other reasons, for example pure coincidence (statistical spread) or ethnic / immunological differences. There were no serious diseases among the vaccinated. Furthermore, the vaccination caused no serious side effects.

Moderna vaccinated 30,000 subjects in the United States, half with a placebo and half with the vaccine. Data processing began two weeks after the administration of the second vaccine dose. To date, 95 people have contracted the virus, 5 of them in the vaccine group and 90 in the placebo group. There have been 11 serious disease courses, none of them in the vaccine group. It therefore appears that the vaccine prevents infections and protects against serious diseases. However, the database is still very small. However, it is also good that no serious side effects have occurred.

According to Biontech’s second press release, 170 of the 41,000 vaccinated people were infected with Sars-CoV-2 from day 7 after receiving the second dose of vaccine (active ingredient or placebo), 162 in the placebo group and only 8 in the vaccine group. . There is no reason for security concerns. The only most frequent and significant side effects are fatigue in 3.8% and headache in 2% of test subjects. Pfizer has already applied for an emergency use authorization with the FDA.

No precise data on the age distribution of the infected have yet been provided. However, Pfizer writes in the press release that in the group of over 65s the effectiveness is greater than 94%. The reliability of this number can only be assessed once the exact age distribution data has been published. Information would be essential, because one of the goals is to vaccinate people at risk first, that is, older people and those with previous illnesses or with weakened immune systems. Often it is these people who develop poor vaccination protection. In the Pfizer and Biontech efficacy study, two age groups were selected, one group between 18 and 55 and one between 56 and 85. Moderna also included people over 65 in the study. However, the two companies did not provide any information on the age of the infected. Since there were only 94 or 95 confirmed infections, very few in the vaccine group, an age-dependent outcome assessment is not meaningful.

It is not clear. To do this, it should not only prevent the disease, but also an infection with an asymptomatic course. If the vaccination protects “only” from severe disease progression, but consequently more people walking with mild or no symptoms, this promotes the spread of the disease. Furthermore, those at risk, for whom even vaccination may not work, are less protected. However, according to experts, the total protection (sterilizing effect) is much more difficult to achieve. The University of Oxford writes that there is evidence that their vaccine can prevent the number of asymptomatic infections and thus the spread of the virus. To verify this, the researchers ran a PCR test on subjects in Britain once a week.

There is still no evidence of this either. In the Biontech / Pfizer efficacy study, researchers measured vaccine protection no earlier than 7 days after the second vaccination dose, 14 days had passed in that of Moderna and the University of Oxford / AstraZeneca. The effects are very likely to wear off over time. How long does immunity last after a Covid-19 infection has been discussed for months. There have been a few cases of secondary infections, but they seem extremely rare. They involved studies that indicated that antibodies decline relatively rapidly after infection. What this means is still not clear enough, especially as recent studies show that the amount of antibodies remains stable for up to six months (provided it was tested in the study).

Protection was achieved after two vaccinations. It is currently unknown whether the vaccination will need to be repeated after two injections. The most common vaccines against other diseases need to be refreshed at regular intervals of several years. Regulatory authorities only approve vaccines that do not cause medical problems. But the issue of refreshments will become acute soon in the next year, when it should become apparent that vaccine protection has already decreased in those who were first vaccinated.

As with all other vaccines, the following also applies here: A statement about rare side effects or harms that occur late can be made if a large number of people have been vaccinated and observed for a long time. Although there has been little experience with mRNA vaccines in general – there is no approved mRNA vaccine yet – but they are considered safe. Contrary to what is sometimes claimed, viral RNA administered in this way cannot integrate into the human genome. It is also rapidly broken down by the body’s enzymes. There is more experience with adenoviruses than with vaccine vectors. These have been studied for many years and are also considered to be very safe. So far, however, no vaccine based on it has proven effective in humans. A rabies vaccine is on the market for wild animals.

It’s hard to say. Some mutations have already occurred and various strains of the virus are circulating around the world. However, there is still no known variant that reduces vaccination success. Furthermore, our immune system always produces different antibodies when vaccinated with an effective vaccine. These are directed against different areas of the viral proteins. Therefore, a vaccination also works against a slightly modified virus. We are also confident that Sars-CoV-2 is genetically much more stable than, for example, flu viruses and is currently changing rather slowly.

Overall, not much. Because the vaccines currently being tested each contain different components of Sars-CoV-2. It is to be expected, however, that those with viral mRNA such as the vaccine candidate from German company Curevac will also have some protective effect. The University of Oxford / AstraZeneca vaccine, on the other hand, is made from Sars-CoV-2 DNA, packaged in a genetic ferry. Other vaccines currently being tested in clinical trials contain inactivated viruses or protein components from the surface of Sars-CoV-2. Each vaccine must demonstrate that its ingredients can trigger an immune response.

Maybe a country in Europe. A few days ago the EU Commission concluded a supply contract with Biontech / Pfizer. If the vaccine is approved, companies want to deliver up to 300 million doses, the European Commission will handle the distribution. Each country should receive vaccine doses in proportion to its population. However, the Biontech vaccine could be approved first in the United States and then delivered there first. Because the US had already ordered 100 million doses in a first tranche in July, while Britain had contractually secured 30 million doses of the vaccine, also in July.

Switzerland has meanwhile agreed a binding reservation of 3 million cans with Biontech / Pfizer, the contract is imminent. By contrast, the federal government had already signed a supply contract with Moderna for 4.5 million cans, as well as with AstraZeneca (5.3 million cans). The EU lags behind Moderna. According to its own information, the EU Commission is currently negotiating with the company for the delivery of up to 160 million doses of the vaccine.

Many countries are currently developing strategies for this. Scientists and ethics experts recommend vaccinating older people and those with previous illnesses first, in case the vaccine is approved for them. Then it would be the turn of doctors and nurses, especially in hospitals and homes. The third group should therefore be represented by people with socially important functions, i.e. teachers, educators, employees of health authorities, police or firefighters.