Breakthrough infections (infections after vaccination) by new variants of SARS-CoV-2 are common, despite the extensive immunization programs against SARS-CoV-2. Recent research suggests that human immune responses change in order to combat the never-ending emergence of new SARS-CoV-2 variants and studies point to memory T cells having a role in protecting individuals immunized with SARS-CoV-2 vaccines against variants.

Now, a team of South Korean scientists reveal that the memory T cells that form during Omicron breakthrough infections respond to subsequent strains of the virus.

This work is published in Science Immunology in the paper, “Omicron BA.2 breakthrough infection elicits CD8+ T cell responses recognizing the spike of later Omicron subvariants.

“This finding gives us new perspectives in the new era of COVID endemic,” said Min Kyung Jung, PhD, research fellow at the Center for Viral Immunology, Korea Virus Research Institute, Institute for Basic Science (IBS). “It can be understood that in response to constant emergence of new virus variants, our bodies have also adapted to combat the future strains of the virus.”

The SARS-CoV-2 Omicron variant drastically increased transmissibility in comparison to its predecessors, which quickly allowed it to become the dominant strain in 2022. New strains (such as BA.1 and BA2, BA.4/BA.5, BQ.1, XBB, and more recently JN.1) of Omicron have emerged since then, leading to widespread breakthrough infection despite vaccination.

The research team’s goal was to uncover the immune system changes that occur after post-vaccination breakthrough infections. They tracked memory T cell responses in a cohort of vaccinated individuals in Korea who experienced BA.2 Omicron subvariant breakthrough infection in early 2022, focusing in on their ability to respond to various Omicron variants such as BA.2, BA.4/BA/5, and more.

The results showed that the memory T cells from these patients had heightened response against not only the BA.2 strain but the later BA.4 and BA.5 strains of Omicron as well. More specifically, they confirmed that “BNT162b2 vaccination induced memory CD4+ and CD8+ T cells specific to BA.4/BA.5 spike, even if these individuals had a prior SARS-CoV-2 infection. Breakthrough infection with early Omicron subvariants (BA.1/BA.2) induced an increase in cross-reactive CD8+ T cell responses specific to BA.4/BA.5 spike.”

In short, the breakthrough infection strengthened the patients’ immune systems to combat future variants. The research team also discovered the specific part of the spike protein that is the primary cause of the observed enhancement in the memory T cells. They wrote that they “identified peptides in the BA.2 spike that were fully conserved in BA.4/BA.5 and later subvariants but absent in original spike.”

These results show that once a person undergoes breakthrough infection by the Omicron infection, it is unlikely for them to suffer severe COVID-19 symptoms from the future emerging variants.

“This new finding can also be applied to vaccine development,” noted Eui-Cheol Shin, MD, PhD, professor at the Korea Advanced Institute of Science and Technology (KAIST) and director of the Center for Viral Immunology at the Institute for Basic Science (IBS). “By searching for common features among the current dominant strain and emerging new strains of viruses, there may be higher chances to induce memory T cell defenses against the subsequent variants.”

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