Incomplete protection? Apparently, not all Covid patients develop protective antibodies after surviving infection, as a study suggests. Accordingly, only 60 percent of those recovered had antibodies that blocked virus binding to the cell. Also surprising: Some plasma samples even promoted the docking of SARS-CoV-2 – and could intensify the infection. This finding is important for future antibody therapies, but also for vaccine research.
In addition to specific immune cells antibody the most effective weapon of our immune system against SARS-CoV-2. The structure of these peptide molecules allows them to bind to the surface proteins of the virus. In the course of the coronavirus infection, the more unspecific IgM antibodies develop first, around three weeks later the IgG antibodies. These only fit a certain section of the viral protein – for example that Spike-Protein of SARS-CoV-2.
Ideally, these highly specific antibodies block the virus from binding to the cell, thereby preventing it from multiplying. Immunologists then speak of neutralizing antibodies. Out dem Plasma Recovered in isolation or made in the laboratory, such neutralizing antibodies can accelerate the healing of Covid-19 patients. They are also considered to be the “protective power” that gives convalescents their immunity to re-infection.
The sicker, the more antibodies
But how reliably do people develop such neutralizing antibodies after a coronavirus infection? And how well do they prevent virus replication? Pia Gattinger from the Medical University of Vienna and her colleagues have now examined this in a patient sample. They tested 25 men and women ten weeks after their Covid 19 disease and healthy controls for IgM and IgG antibodies.
It turned out that in principle all patients had both IgM and IgG antibodies against the surface proteins of SARS-CoV-2 in the blood. The proportion of antibodies that matched the binding site of the viral spike protein was higher, the more pronounced and long-lasting the symptoms of Covid-19 had been. “This indicates that a longer illness and higher viral load increases the production of virus-specific antibodies,” say the researchers.
But protective effect only at 60 percent
However, there is a limitation, as a supplementary experiment revealed. In this test, the scientists tested how effectively their test subjects’ antibody-containing plasma samples prevent the coronavirus protein from docking to the ACE2 receptor on human cells. The surprising result: the antibodies in plasma only developed this protective effect in 60 percent of the patients. In contrast, 40 percent of the subjects did not have this goat effect.
“Our data suggests that normal SARS-CoV-2 infection does not trigger a protective antibody response in all infected people that prevents the virus from docking to the receptor,” said Gattinger and her colleagues. It cannot be ruled out that these patients may produce other types of antibodies that also have a certain protective effect. However, they lacked the classic immunoglobulins that bind to the virus.
Virus attachment promoted instead of blocked
And not only that: In five of the recovered Covid 19 patients, the antibodies in the plasma even promoted the binding of the viral binding protein to the ACE2 receptor. “This is the first study to demonstrate such an increase in ACE2 accumulation by the plasma of convalescents,” the researchers state. This effect occurred even though these patients had specific antibodies against the binding site on the spike protein of SARS-CoV-2.
“This is the first study that shows increased binding to ACE2 through immune complexes consisting of the viral binding protein and patient antibodies,” explains study leader Rudolf Valenta from the Medical University of Vienna. “This potentially makes it even easier for the virus to settle and spread.”
Antibody aggravation?
This could mean that the antibodies made by these patients actually promote virus replication rather than blocking it. There is an effect behind this, which scientists call “antibody-dependent enhancement“(ADE) designate. This docking antibody does adhere to the surface of the virus, but only leads to clumping, during which the virus can nevertheless enter the cell. The protruding ends of the antibodies provide the entry key for this.
Further research should now find out what exactly that means for immunity and vaccine development. This finding could also be important for the development of possible antibody therapies against SARS-CoV-2. (Allergy, 2020; doi: 10.1111/all.14523)
Source: Medical University of Vienna
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