For T-cells, omicron is nothing unusual

From the start, the omicron variant had experts worried because its version of the virus's spike protein carried mutations in many of the sites that are recognized by antibodies. This meant that antibodies generated to combat earlier variants like delta were less likely to recognize the newcomer. The fears have played out in the form of lowered immunity to omicron and the failure of some antibody-based therapies.

But all the worries were focused on the immune system's antibody response. The immune system also produces T-cells that recognize the virus, and wasn't clear how omicron affected their response. Based on two recently published papers, the answer is "not much at all," which could help explain why the vaccines continue to protect from severe disease.

Those other cells

The T-cell-based immune response works very differently from that of antibody-producing cells. It relies on the fact that all cells chop up a small fraction of the proteins they make. Specialized proteins then grab on to some of the resulting protein fragments and display them on the cell's surface. Once on the surface, they can be recognized by a receptor on the surface of T-cells.

The immune system gets rid of any T-cells that recognize proteins normally made by human cells. But when a pathogen is present, cells will start displaying some of its proteins on their surface. T-cells can recognize these proteins as foreign and trigger a number of responses. Helper T-cells make signaling molecules that rev up other immune cells, including those that make antibodies. Killer T-cells can latch on to the surface of infected cells and kill them.

T-cells are essential for the immune response; the absence of helper T-cells is what causes the immune deficiency seen in AIDS patients. But their role in fighting off SARS-CoV-2 was less clear, as protection from infection was largely correlated with levels of antibodies.

The lack of clarity was made worse by the fact that T-cells are hard to study. A simple blood sample is all we need to obtain enough antibodies to see what they stick to. T-cells can also be obtained from a blood sample, but they must be grown in culture for weeks to get a sense of what they might be responding to.

Nevertheless, two different groups have obtained T-cells from a combination of vaccinated and infected individuals and have tested the T-cells for their response to omicron.

Different studies, similar results

One of the studies was done in South Africa, where omicron was first characterized. A research team obtained T-cells from patients vaccinated using either the J&J or Pfizer/BioNTech vaccines or from unvaccinated people who previously had COVID-19. Each group had 15–20 individuals. These T-cells were then exposed to fragments of the omicron spike protein and tested to see whether the cells responded.

Overall, both helper and killer T-cell responses were reduced when they were exposed to omicron's version of the spike. But the reduction was not dramatic—roughly 70-80 percent of the original response persisted. There were a few individuals in which killer T-cell responses were completely absent, but the helper T-cells didn't seem to suffer from this issue. And many of the individuals had a strong T-cell response to omicron despite having their antibody response severely reduced.

The second study took place in Boston, where researchers again worked with people who had received either the J&J or Pfizer/BioNTech vaccines roughly eight months earlier. Again, killer T-cell responses to omicron remained high, with J&J recipients showing responses to omicron that were over 80 percent of their response to the ancestral strain for which the vaccine was designed. (Responses to the delta variant were indistinguishable from the response to the ancestral strain.) For the Pfizer/BioNTech vaccine, the drop-off against omicron was even smaller. Helper T-cells saw no drop-off in their response to omicron at all.

When looking at memory T-cells, which help preserve the immune response for long periods, the news was even better. For both vaccines and for both helper and killer cells, there was no drop-off with omicron. The response to omicron was indistinguishable from the response to the viral strain that the vaccine was designed against.

In for the long haul

On the simplest level, the data tells us that the pieces of the spike protein that are recognized by T-cells don't overlap much with the things that are recognized by antibodies. This means a far larger number of mutations would be needed to avoid both types of immunity. And because omicron can clearly cause infections in people with a strong T-cell response, it's not clear whether there's going to be a strong evolutionary selection for the sorts of mutations that could allow the virus to escape T-cell recognition.

These infections, however, don't tend to progress to symptoms severe enough to require hospitalization, even though the antibody response to omicron appears to be severely compromised by its many mutations. This suggests that (as is seen in other diseases) T-cells might be playing a role as backstop to the antibody response—able to limit an infection if one gets started but not able to block the infection entirely.

We'll need a lot of additional data before we learn the precise role of T cells during SARS-CoV-2 infections. But if these results turn out to be accurate, they are very good news, given that they show the T-cell response is extremely stable over time.

Nature, 2022. DOI: 10.1038/s41586-022-04465-y, 10.1038/s41586-022-04460-3 (About DOIs).