A recent study found that vaccination with two doses of the Pfizer-BioNTech COVID-19 vaccine resulted in immune cell response considerably lower in people with prior SARS-CoV-2 infection than those without.

The level of this key immune cell that targets the SARS-CoV-2 spike protein, CD8+ T, was substantially lower in unvaccinated people with COVID-19 than in vaccinated people who had never been infected. People who recover from SARS-CoV-2 infection and then get vaccinated are more protected than people who are unvaccinated and the new paper suggests that the virus damages an important immune-cell response.

The investigators studied CD4+ and CD8+ T-cell responses in blood samples from three groups of volunteers. One group had never been infected with SARS-CoV-2 and received two doses of the Pfizer-BioNTech COVID-19 vaccine. The second group had previously been infected with SARS-CoV-2 and received two doses of the vaccine. The third group had COVID-19 and was unvaccinated.


Colorized scanning electron micrograph of a T cell. Credit: NIAID

The researchers found that vaccination of people who had never been infected with SARS-CoV-2 induced robust CD4+ and CD8+ T-cell responses to the virus’ spike protein. In addition, these T cells produced multiple types of cell-signaling molecules called cytokines, which recruit other immune cells—including antibody-producing B cells—to fight pathogens. However, people who had been infected with SARS-CoV-2 prior to vaccination produced spike-specific CD8+ T cells at considerably lower levels—and with less functionality—than vaccinated people who had never been infected.

The researchers observed substantially lower levels of spike-specific CD8+ T cells in unvaccinated people with COVID-19 than in vaccinated people who had never been infected. 

Taken together, the investigators write, these findings suggest that SARS-CoV-2 infection damages the CD8+ T cell response, an effect akin to that observed in earlier studies showing long-term damage to the immune system after infection with viruses such as hepatitis C or HIV. The new findings highlight the need to develop vaccination strategies to specifically boost antiviral CD8+ T cell responses in people previously infected with SARS-CoV-2, the researchers conclude.