January 26, 2022

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Cellular immunity, a valuable ally in the fight against omigran

It is now well established that the Omigron variant is less sensitive to antibodies produced by two doses of the Govit-19 vaccine. Fortunately, studies indicate that the other aspect of immunity is not affected by mutations in the cellular immune system, which helps maintain better protection against severe forms of the disease. While this is undoubtedly a staggering increase in the number of new positive cases, there is a small increase in the number of hospital admissions, mainly among vaccinated people.

Antibody resistance

Antibodies are a key component of the immune response induced by the vaccine against Covit-19: by binding to certain parts of the S protein (epitopes) on the surface of the corona virus, the antibodies neutralize the circulating virus, thereby significantly reducing the severity of infection and / or disease.

Large numbers of people have these neutralizing antibodies, whether they have been vaccinated or have been infected with the virus in the past. This high prevalence of antibodies creates a great deal of evolutionary pressure on the corona virus to select mutations that allow the immune system to escape this neutralization.

The most recent Omigran variant represents a truly gigantic leap in acquiring this ability for viral immunity: studies so far have indicated a very strong reduction (30-fold and plus) neutralization by antibodies. Made with all current vaccines(1).

The amazing speed at which this variant is currently spreading worldwide makes it clear that the combination of these mutations has significant evolutionary benefits for the virus and that this variant is expected to become the main form of the corona virus that spreads in the short term.

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Vaccines are more effective than anything else

The high resistance of the omigran variant to antibodies apparently affects the effectiveness of the vaccine, but much less than initially feared. For example, data collected in South Africa show that wherever the omigran variant appears, the vaccine reduces the risk of serious complications from COVID-19 by 70% and that vaccinated people are generally much less likely to be infected. Cases seen in previous waves(2).

The third dose (booster) of MRNA vaccines greatly compensates for the loss of immunity and makes it possible to obtain the same protection against the original virus strain, i.e. approximately 90%. People at high risk for complications from COVID-19, whether due to age or the presence of co-morbidities, can adequately protect themselves from the Omicron variant with the third dose vaccine.

Cellular immunity of killer cells

Despite the decrease in antibody neutralization activity, this protection against omigran may be due to the activity of D lymphocytes, the immune system does not lay all its eggs in one basket: at the same time, the vaccine activates a battalion. D-lymphocytes capable of neutralizing the virus: This is called cellular immunity. Some of them, called killer T cells (or CD8 + T cells), directly destroy infected cells. Others, called helper D cells (or CD4 + D cells), are important for a variety of immune functions, including stimulating the production of antibodies and killer T cells.

Two characteristics of D lymphocytes are that they are very important in combating the virus we are currently facing:

  1. These cells have long memories: after activation by the virus (following vaccination or infection), some clones retain the memory of the presence of the virus and reactivate quickly in the event of a new infection. According to a recent study, this T-cell memory is still active for more than a year after being infected with the corona virus.(3).
  2. T cells target different parts of the virus that are recognized by antibodies, and these recognized sites may vary from person to person. As a result, there are a wide variety of T cells in the population capable of neutralizing the virus, making it very difficult to select mutations that allow the virus to escape from this cellular recognition. Furthermore, it has recently been demonstrated that most of the epitopes recognized by D lymphocytes are different from mutations in the Omigron variant and, as a result, do not interfere with the mediation of D cells.(4).
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Thus, the general picture of immunity to Omigran looks as follows: On the one hand, as the effectiveness of antibodies against Omigran decreases, the immune system is less likely to neutralize the virus through circulation, which reduces the effectiveness of vaccines against infections. For this variation (this efficacy can be seen with the third dose).

D cells, on the other hand, cannot prevent infection because they kick in after a virus has invaded our cells. However, since they are not affected by viral mutations, they retain the removal properties of infected cells, thus preventing the virus from spreading throughout the body. The net result is that in most cases the infection is maintained in a mild state and there is no progression of the disease to the severe stages that require hospitalization.

(1) Cameron E. et al. Broadly neutralizing antibodies inhibit SARS-CoV-2 Omicron antigenic mutation. bioRxiv, pre-filed on December 14, 2021.
(2) https://www.discovery.co.za/corporate/news-room
(3) Adamo S et al. Signature of chronic memory CD8 + T cells in acute SARS-CoV-2 infection. Nature, released December 7, 2021.
(4) Redd AD and coll. Minimal cross-over between mutations associated with the omigran variant of SARS-CoV-2 and CD8 + T cell epitopes was identified in COVID-19 cured individuals. bioRxiv, déposé en publication on 9 December 2021.