By Zania Stamataki
The antibodies we create after being infected with or vaccinated against a virus can be very powerful.
A virus usually spreads around our body by entering a cell and using it as a factory to create copies of itself, which then burst and find new cells to infect.
Our antibodies work by binding to the virus, which can prevent it from attaching itself and entering our cells in the first place.
But what if a virus doesn’t need to come out of the cell to spread to neighboring cells? Can our antibodies be effective against it?
Scientists recently asked this question for SARS-CoV-2, which causes Covid-19. This highly infectious coronavirus can modify human cells, causing them to fuse with two or more neighboring cells. These super cells, with large fused cell bodies, are excellent viral factories.
Supercells, known as syncytia, share multiple nuclei (the part of the cell that contains genetic material) and abundant cytoplasm (the gelatinous substance that surrounds the nucleus).
Having more of these components in a giant cell helps the virus to replicate more efficiently. And by fusing the cells, SARS-CoV-2 increases its resources without being exposed to the neutralizing antibodies that spread outside our cells.
The study by Alex Sigal and his colleagues tested two variants of the coronavirus (alpha and beta) for their ability to be transmitted from cell to cell and examined whether this mode of transmission was sensitive to neutralization of antibodies. The alpha variant (first identified in the UK) is sensitive to antibodies and the beta variant (first identified in South Africa) is less sensitive to these antibodies.
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The Sigal study, which has not yet been published in a scientific journal, found that cell-to-cell transmission with both variants managed to escape neutralization of antibodies. This shows that when the virus sets in, it will be more difficult to eliminate in cells which can fuse with each other.
Viruses have coexisted with humans and animals for millennia, so they have developed tricks to avoid being recognized by our immune system. One such strategy of immune evasion is direct cell-to-cell transmission, which does not always require cell fusion.
It is also possible for viruses to travel to their next host cells by exploiting close associations between neighboring cells that protect them from antibodies. It is reasonable to assume that antibodies are most effective in preventing entry into the host cell and less effective in parts of the body where infection is already established.
Does this mean that our vaccines will be ineffective against viruses that move directly from cell to cell? Fortunately, our immune systems have also evolved along with viruses, and we’ve learned to build defenses that work in many ways.
Not the only line of defense
T cells are white blood cells which, after vaccination or infection, are trained to recognize and kill infected cells. They don’t rely on recognition of floating viruses, so cell-to-cell transmission doesn’t reduce their ability to find and destroy viral factories. Like cells capable of making antibodies, T cells can remember a previous infection and act quickly when the same virus reappears.
It is not wise to put all your eggs in one basket, which is why vaccines induce both antibodies and virus-specific T cells. Antibodies bind to viruses either before they enter our cells or after new viruses are released from infection. T cells work to shrink fertile cell hosts for virus replication, until the infection is cleared. Many other cells (without immunological memory) also work together to completely eradicate the virus from the body.
What happens to those of us who may have older or dysfunctional parts of our immune system? Coronavirus infection is usually controlled within two weeks in most healthy, young adults and children.
In people with dysfunctional T cell responses, cell-to-cell transmission may interfere with neutralization of antibodies and therefore prolong infection. Persistent infection increases the opportunities for viruses to mutate and better adapt their life cycle to our body, leading to the potential emergence of variants of concern.
We don’t have to worry about cell-to-cell transmission disabling our vaccines, but it is important to understand how a virus spreads so that we can target it more effectively. A few years ago, my colleagues and I showed that the hepatitis C virus is transmitted from cell to cell in the presence of neutralizing antibodies. That hasn’t stopped scientists from developing highly effective antivirals that can cure people infected with hepatitis C for decades.
With effective vaccines and antivirals, we can aim to eradicate viruses that do not integrate their genome into our own (like SARS-CoV-2) from human populations as we have done before. Broad resistance to infection in humans achieved by vaccination if we all work together means that if the same virus jumps out of animal hosts again, its route of transmission in humans would be very short. The latest technologies that allow rapid vaccine updates can provide effective control against emerging variants.
(The author is Senior Lecturer in Viral Immunology, University of Birmingham)