Sunday, March 21, 2021

How SARS-CoV-2 evades immune system defenses

Very recommendable! This research seems to suggest that targeting the viral spike is probably not good enough and that repeated vaccinations may be necessary! Hopefully, this intense global research on SARS-CoV-2 will lead to better vaccinations/treatments against e.g. the flu and the common cold!

"he vast majority of people infected with SARS-CoV-2 clear the virus, but those with compromised immunity — such as individuals receiving immune-suppressive drugs for autoimmune diseases — can become chronically infected. ...
The research, published March 16 in Cell, shows that a mutated SARS-CoV-2 from a chronically infected immunocompromised patient is capable of evading both naturally occurring antibodies from COVID-19 survivors as well as lab-made antibodies now in clinical use for treatment of COVID-19. ...
Interestingly, the [chronically infected immunocompromised] patient-derived virus contained a cluster of changes on its spike protein —  the current target for vaccines and antibody-based treatments — and
some of these changes were later detected in viral [variant] samples in the U.K. and South Africa, where they appear to have arisen independently, the researchers said. ...
Some of the changes found in the patient-derived virus have not been identified yet in dominant viral variants circulating in the population at large. ...
The researchers emphasize that variants initially detected in the U.K. and South Africa remain vulnerable to currently approved mRNA vaccines, which target the entire spike protein rather than just portions of it. Nonetheless, the study results could also offer a preview into a future, in which current vaccines and treatments may gradually lose their effectiveness against next-wave mutations ...
the need to design next-generation vaccines and therapies that target less mutable parts of the virus. ...
[researchers] created lab-made, noninfectious replicas of the patient virus that mimicked the various structural changes that had accumulated in the span of five months.

In a series of experiments, the researchers exposed the dummy virus to both antibody-rich plasma from COVID-19 survivors and to pharmaceutically made antibodies now in clinical use. The virus dodged both naturally occurring and pharmaceutical-grade antibodies.

Experiments with a monoclonal antibody drug that contains two antibodies showed the virus was entirely resistant to one of the antibodies in the cocktail and somewhat, although not fully, impervious to the other. The second antibody was four-times less potent in neutralizing the mutated virus. ...
In a final experiment, the researchers created a super antibody by cobbling together proteins from naturally occurring antibodies that had evolved over time to become more attuned to and better at recognizing SARS-CoV-2 and capable of latching onto it more tightly. The process, known as antibody affinity maturation, is the principle behind vaccine booster shots used to fortify existing antibodies. One specific variant containing mutations that had occurred late in the course of the patient’s infection was capable of withstanding even this super-potent antibody. But the super-potent antibody did manage to neutralize viral mutations detected at a different time in the course of the infection. ...
Long-term, this means that scientists should pivot toward developing therapies that go beyond antibody immunity and include also so-called cellular immunity, which is driven by T cells — a separate branch of the immune system that is independent of antibody-based immunity."

How SARS-CoV-2 evades immune system defenses – Harvard Gazette Highlights need for vaccines to aim at multiple targets to minimize risk of resistance

Here is the links to the underlying research paper:

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