Antibodies are crucial for vaccination to work, but scientists don’t yet know what level they must reach. The new delta variant poses another problem.
After a coronavirus infection or a vaccination, the body produces antibodies against the virus’s spike protein, which SARS-CoV-2 uses to dock onto the cells and penetrate them. This spike protein allows antibodies to recognize the virus and bind to it, making it visible to immune cells.
Scientists previously assumed that people vaccinated with mRNA vaccines such as the one produced by BioNTech-Pfizer had more than 90 per cent protection against the virus – but that does not apply to the new delta variant. This variant is much more contagious than the ancestral virus and is spreading all over the world.
Carsten Watzl, an immunologist at the Leibniz Institute of the Dortmund Technical University, estimates that the effectiveness of BioNTech-Pfizer mRNA vaccines has reduced from 90 per cent, in the case of the original virus, to 88 per cent with delta. The AstraZeneca vector vaccine’s effectiveness has gone from 66 per cent to 60 per cent.
Data from Israel indicates that protection against infection with the dangerous variant is only about 64 per cent when the BioNTech-Pfizer vaccine is used. But the vaccine still offers 93 per cent protection against a severe case of Covid-19. The Israeli Health Ministry is now considering offering people a third dose of the vaccine.
After two shots, the majority of the people are immune to the virus variants known so far – but Carsten Watzl cautions that this does not necessarily apply to everyone who is double-vaccinated.
“Vaccination alone is no guarantee for being immune,” he says, adding that what matters is whether the body has built up sufficient immune protection. “But we can’t measure that at the moment,” he says.
This is different from a tetanus vaccination, where tests can determine whether or not a body is sufficiently protected. A lab checks the blood for the level of antibody titers. If the number of antibodies is above a certain threshold, the person is immune to the tetanus virus. If the titer is too low, the patient needs a booster shot.
With the coronavirus, researchers have not yet reached that stage, Watzl says. “We don’t know yet exactly what we need to measure to really determine whether someone is immune or not. Presumably, the neutralizing antibodies play a key role – they bind the virus in such a way that it cannot infect any more cells.”
But it is unclear how high the number of these antibodies has to be, he adds.
What do the T cells do?
Only antibodies are not essential in the fight against infection. Once the virus has entered the cell, the antibodies can no longer reach it, because they cannot go into the cell. So, the virus will replicate.
“To fight that, our immune system has T cells; they are able to kill such virus-infected cells – in other words, we would rather sacrifice a few cells in our body, namely the infected ones, than give the virus the opportunity to multiply,” Watzl says.
Both these processes can be measured. In practice, however, it is more difficult to determine the number of T cells than that of antibodies. The T cell test is relatively time-consuming but quite useful.
“The antibodies alone don’t necessarily tell you anything about how well you are protected,” says Watzl: He says that a person might have hardly any antibodies and so could still become infected with the virus. “But the response of the T cells is so strong that the person doesn’t get seriously ill,” he says.
People with a high level of antibodies are probably well protected against the coronavirus, the immunologist added. But the reverse conclusion – that few antibodies mean no protection – is probably not true, according to him.
A matter of levels
Coronavirus antibody tests employ various measurement methods. Normally, laboratory tests use a clear standard stipulating a minimum to a maximum value. This allows a doctor to see whether levels are within the normal range. The levels have not yet been defined for the coronavirus, however.
So, doctors approximate, with measured levels ranging from less than a hundred to several thousand antibodies. “If I am in the upper third or in the upper half, I probably have good immune protection. But I can’t give you the exact threshold values yet,” Watzl says.
It is not clear how quickly antibody levels drop, only that they do drop over time.
“It moves in two waves – if you look at the levels right after vaccination, you have the highest antibody level. In the first few months after vaccination, that level decreases relatively quickly. At some point, the whole thing settles at a certain value, and only drops very slowly from there,” Watzl says, adding that scientists are familiar with this phenomenon from other vaccinations. “It appears to be true for the coronavirus vaccine, too; science just hasn’t proven that yet,” he says.
More is better
Some people who have been vaccinated twice have hardly any antibodies against the virus, so they are probably not properly protected, warns Watzl. Low antibody levels can be due to age or a suppressed immune system. Often patients need a third vaccination for the body to form antibodies at all.
Observations range from people who have many antibodies and are well protected to people who have too few antibodies and are poorly protected to people with few antibodies who are still protected.
The conclusion so far is that no one knows for sure. But Watzl is optimistic, emphasizing that “more is better.”
“We don’t know yet what the threshold levels are, and what level it takes to be protected,” he says. “But we will get there someday.”