This Is What Vaccines Do In Your Body To Paralyze

This is what vaccines do in your body to paralyze Covid-19

The drugs promote that we develop a robust defense against virus infection with great efficiency.

A health worker administers a vaccine in Andalusia.

All the vaccines approved so far to fight Covid-19 follow a common strategy: they present the SARS-CoV-2 protein S to our adaptive immune system. In this way encourage us to develop a robust defense against virus infection. And they all have comparable efficacy when it comes to preventing severe Covid and death.

What distinguishes them then? That a few modifications in the protein S of some vaccine formulas cause it to slightly stimulate better production of neutralizing antibodies, which may improve the vaccine’s ability to prevent infection and its symptoms.

To understand why, we must start by knowing that the surface protein S of SARS-CoV-2 has two essential functions in the biology of the virus: mediate binding to the cell to be infected and mediate fusion of virus and cell membranes.

On the surface of the virus, the S protein functions as an anchor by binding to the ACE2 protein and co-receptor proteins such as NRP1 on the cell to be infected. But nevertheless, this tethering function keeps the protein in a rigid state, in which it is unable to fuse to release its genome into the cell it is infecting.

To take the second step and complete the fusion of the virus, the S protein needs to be partially cleaved by proteases such as TMPRSS2 or Cathepsin L. These molecular scissors allow part of the receptor-anchored S protein to be released. Once released, internal fragments called fusion peptides they are fired like harpoons and bind to the membrane of the cell to be infected.

Subsequently, the S protein refolds and forces the virus and cell membranes closer together. Until they end up merging to release the virus genome into our cells. Invasion over!

During the process of cutting and releasing the fusion peptides, the S protein changes shape, and this limits the stimulation of neutralizing antibodies.

In order to achieve better immunization, vaccines such as those from Janssen, Pfizer-Biontech, Moderna or Novavax, but not others such as AstraZeneca AZD1222, Coronavac or Sputnic V, are capable of expressing the S protein with changes that prevent it from being cut and advance to its melted state. This kind of spatial “freezing” increases the capacity immunostimulatory for the generation of neutralizing antibodies and immune protection against the virus.

The strategy of modifying the surface proteins of a virus to prevent it from being cut by proteases and from carrying out the fusion process is being used for development of other vaccines. Among them, the vaccine against respiratory syncytial virus, on which work has been carried out for more than 60 years, the vaccine against influenza or AIDS viruses.

It should be kept in mind that it is the basic knowledge of the mechanisms that govern the infection of a virus –in this case, of the fusion processes– that have allowed the development of vaccine strategies such as the one mentioned.

Investing in the generation of knowledge, therefore, is an essential tool for dealing with both the unknown and the known that pose unresolved problems.

*This article was originally published on The Conversation.

**Estanislao Nistal is a virologist and professor of Microbiology at the Faculty of Pharmacy.