Evolution of the human immune system in the post-Omicron era

It has been 4 years since the start of the COVID-19 pandemic. SARS-CoV-2 has yet to be eradicated and new variants are continuously emerging. Despite the extensive immunization programs, breakthrough infections (infection after vaccination) by new variants are common. New research suggests that human immune responses are also changing in order to combat the never-ending emergence of new SARS-CoV-2 variants. Specifically, it has been discovered the immune system that encountered breakthrough infection by the Omicron variant acquires enhanced immunity against future versions of the Omicron.

A team of South Korean scientists led by Professor SHIN Eui-Cheol of the Korea Virus Research Institute Center for Viral Immunology within the Institute for Basic Science (IBS) announced that the memory T cells that form during the Omicron breakthrough infection respond to subsequent strains of the virus.

Emerging in late 2021, the SARS-CoV-2 Omicron variant had drastically increased transmissibility in comparison to its predecessors, which quickly allowed it to become the dominant strain in 2022. New strains of Omicron have kept emerging ever since then. Starting with BA.1 and BA2, BA.4/BA.5, BQ.1, XBB strains, and more recently JN.1 strains were among the new strains of the Omicron variant. This has led to widespread breakthrough infection despite vaccination.

After becoming infected or vaccinated, the body creates neutralizing antibodies and memory T cells against the virus. The neutralizing antibody serves to prevent host cells from being infected by the virus. While memory T cells cannot prevent the infection, they can quickly search and destroy infected cells, preventing the viral infection from progressing into a severe disease.

The research team selected patients who suffered then recovered from BA.2 Omicron breakthrough infection in early 2022 as subjects and conducted studies on their memory T cells, specifically in their ability to respond to various Omicron variants such as BA.2, BA.4/BA/5, and others. In order to do so, immune cells were separated from the peripheral blood of the subjects, and the memory T cells' cytokine production and anti-viral activities in response to various spike proteins from different variants were measured.

The results showed that the memory T cells from these patients showed heightened response against not only the BA.2 strain but the later BA.4 and BA.5 strains of Omicron as well. By suffering from breakthrough infection, these patients' immune system was strengthened to combat future strains of the same virus. The research team also discovered the specific part of the spike protein which is the primary cause of the observed enhancement in the memory T cells. These results show that once a person undergoes breakthrough infection by the Omicron infection, it is unlikely for them to ever suffer severe COVID-19 symptoms from the future emerging variants.

Reference: Evolution of the human immune system in the post-Omicron era; Science Immunology;DOI: 10.1126/sciimmunol.adg8691