It is now well established that the Omicron variant is less sensitive to the antibodies generated by the two doses of the COVID-19 vaccines. Fortunately, studies indicate that the other aspect of immunity, cellular immunity, does not appear to be affected by mutations in the variant, which helps maintain excellent protection against more severe forms of the disease. This would undoubtedly explain that despite the dazzling increase in the number of new positive cases, there is little increase in hospitalizations, in populations mainly vaccinated.
Antibody resistance
Antibodies are an important facet of the immune response induced by vaccination against COVID-19: by binding to certain regions (epitopes) of the S protein present on the surface of the coronavirus, the antibodies can neutralize the circulating virus and thus prevent infection and / or significantly reduce the severity of the disease.
A very large number of people have these neutralizing antibodies, either because they have been vaccinated or because they have been infected with the virus in the past. This high prevalence of antibodies therefore creates an enormous evolutionary pressure on the coronavirus to select mutations that could allow it to escape this neutralization by the immune system.
The Omicron variant, which appeared very recently, seems to represent a real giant leap in the acquisition of this capacity for immune evasion by the virus: the studies carried out so far indeed indicate a very strong reduction (30 times and plus) neutralization by antibodies generated by all current vaccines(1).
The phenomenal speed with which this variant is currently spreading globally clearly shows that this combination of mutations has a marked evolutionary advantage for the virus and that this variant is expected to become the main form of the circulating coronavirus in the short term.
Vaccines still effective despite everything
The greater resistance of the Omicron variant to antibodies obviously affects the effectiveness of vaccines, but much less than initially feared. For example, data collected in South Africa, the place where the Omicron variant seems to have emerged, indicate that the vaccine reduces the risk of severe complications from COVID-19 by 70% and that those vaccinated generally appear to be very less sick than the cases observed in previous waves(2).
It has also been shown that a third dose (booster) of mRNA vaccines makes it possible to largely compensate for the loss of immune efficiency and to obtain protection similar to that observed against the original viral strain, i.e. around 90%. People at higher risk of complications from COVID-19, either because of age or the presence of co-morbidities, can therefore adequately protect themselves from the Omicron variant with a third dose of the vaccine.
Cellular immunity of killer cells
This protection observed against the Omicron, in spite of a declining antibody neutralization activity, is most likely due to the action of T lymphocytes. The immune system does not put all its eggs in the same basket: at the same time against antibodies, vaccination activates a battalion of T lymphocytes which also have the capacity to neutralize the virus: this is called cellular immunity. Some of them, known as killer T cells (or CD8 + T cells), outright destroy cells infected with the virus. Others, called helper T cells (or CD4 + T cells) are important for various immune functions, including stimulating the production of antibodies and killer T cells.
Two characteristics of T lymphocytes make them particularly important for fighting a virus like the one we are currently facing:
- These cells have long memories: after being activated by the virus (either by vaccination or following an infection), some clones retain the memory of the presence of the virus and can be quickly reactivated in the event of a new infection. This T cell memory is still active more than a year after infection with the coronavirus, according to a recent study.(3).
- T cells target different portions of the virus from those recognized by antibodies, and these recognized sites may be different from person to person. As a result, a wide variety of T cells capable of neutralizing a virus are present in a population, which makes it very difficult to select for mutations that can allow the virus to escape this cellular recognition. Moreover, it has recently been shown that the vast majority of epitopes recognized by T lymphocytes are different from the mutations present in the Omicron variant and that, consequently, these mutations do not interfere with the neutralization mediated by the T cells.(4).
The general portrait of immunity to Omicron therefore seems to be as follows: on the one hand, the decrease in the effectiveness of antibodies against Omicron means that immunity is less able to neutralize the virus by circulation, which reduces the effectiveness of vaccines against infections due to this variant (this effectiveness can however be found with a third dose).
T cells, on the other hand, cannot prevent infection because they only kick in after a virus has infiltrated our cells. However, since they are not affected by virus mutations, they retain the property of eliminating cells infected with the variant and thus prevent the virus from spreading inside the body. The net result is that in the majority of cases the infection is maintained in a mild state, with no progression of the disease to severe stages requiring hospitalization.
(1) Cameroni E et al. Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift. bioRxiv, filed in prepublication on December 14, 2021.
(2) https://www.discovery.co.za/corporate/news-room
(3) Adamo S et al. Signature of long-lived memory CD8 + T cells in acute SARS-CoV-2 infection. Nature, published December 7, 2021.
(4) Redd AD et coll. Minimal cross-over between mutations associated with Omicron variant of SARS-CoV-2 and CD8+ T cell epitopes identified in COVID-19 convalescent individuals. bioRxiv, déposé en prépublication le 9 décembre 2021.