Retargeting vaccines?

Human antibodies recognize different coronaviruses

Kirill Stasevich, Science and Life (nkj.ru )

When a pathogenic virus or bacterium invades us, the immune system begins to synthesize antibodies – special proteins that recognize the pathogen. What do you mean they find out? Antibodies bind to microbe-specific molecules; in the case of a virus, such a molecule would be some kind of viral protein. When antibodies stick to a viral protein, firstly, the protein itself becomes unable to perform its harmful functions, and secondly, immune cells see a target marked with antibodies and try to destroy it.

But antibodies do not recognize the entire viral protein as a whole, but only a part of it, a small structural fragment. Viruses, as you know, mutate quite easily. Changes appear in viral proteins that do not interfere with their work in any way and at the same time make them invisible to antibodies. Of course, then the immune system will realize that the virus is eluding it, and we will have a new edition of antibodies – now they will work against a new strain of the virus. But until they appear, this strain can cause a lot of trouble. Again, if we want to create a vaccine against the virus, we have to act with an eye to the fact that the virus will change, that it will have a new version, and that the old vaccine will be useless.

In the case of the new coronavirus SARS-CoV-2, most diagnostic tests and available vaccines are focused on the so-called S-protein. It sits in the shell of the virus and helps it to enter the cell. The S-protein is extremely important for the virus, but at the same time, new mutations easily appear in the S-protein that do not prevent the virus from entering the cells. Accordingly, the question arises as to how effective a vaccine that targets immunity to the S-protein will be. Of course, here you can think about taking into account different variants of the S-protein when creating a vaccine, so that the immune system can recognize not just one strain, but several strains of the virus at once.

But there are others besides the S-protein in the viral envelope. For example, the N-protein, or nucleocapsid protein, is associated with the RNA of the virus, in which all its genes are stored. It is a protein packer that helps to pack RNA into a compact form inside the viral particle and at the same time protects RNA from some adverse effects. Staff The University of Pennsylvania writes in the journal Nanoscale shows that the N-protein is surprisingly constant among different types of coronaviruses. The researchers compared the amino acid sequences and three-dimensional structures of the N-proteins of the SARS-CoV-2, SARS-CoV-1, MERS-CoV viruses (which caused the outbreak of a very dangerous Middle Eastern acute respiratory syndrome in the 2010s). To human coronaviruses, those that live in bats, pangolins and civets were added – all these animals serve as a natural reservoir of coronavirus and it is from them that viruses are believed to have jumped to humans.

In a viral particle, N-proteins are hidden in its depth, under the shell, but during infection, N-protein molecules float freely in the blood, where they can be seen by immune cells; obviously, N-proteins can also appear on the surface of cells infected with the virus – cells usually exhibit fragments of proteins that they have inside, so that the immune system can distinguish a sick cell from a healthy one. That is, the immune system is quite capable of creating antibodies against the N-protein, and it does create them. N-proteins of different viruses mutate, like other viral proteins, and differ in some ways from each other. But the part of the molecule for which the antibodies grab them is surprisingly constant in N-proteins. That is, antibodies against the N-protein of the SARS-CoV-2 virus can recognize the N-protein of the MERS virus or the virus taken from the pangolin. We are talking specifically about human antibodies: the researchers took blood samples from COVID-19 patients for the experiment.

Here it can be noted that the authors of the work still did not compare the N-proteins of different strains of the SARS-CoV-2 coronavirus. However, if these proteins are the same in different types of coronaviruses, then it can be assumed that in different strains within the same species (that is, in different strains of SARS-CoV-2) they will all the more be the same – in the sense that they will have the same areas for which they are grabbed by antibodies. If you create a vaccine, after which the immune system will recognize exactly the N-protein, then with its help you will be able to protect yourself from many viral strains at once. Although, of course, for reliability, you still need to check what the N-proteins look like in new strains of SARS-CoV-2, which we have been hearing about more and more recently.

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