Vaccine recipients who were previously infected with SARS-CoV-2 did not have as robust a response to two shots as did those who had never been infected.

That is according to a recent report in the journal Immunity. Stanford University–led researchers found that the magnitude and quality of a key immune cell’s response to vaccination with two doses of the Pfizer-BioNTech COVID-19 vaccine were considerably lower in SARS-CoV-2 infection survivors compared with those who never had been infected.

The level of this key immune cell that targets the SARS-CoV-2 spike protein was also significantly lower in those never-vaccinated with COVID-19 than in vaccinated people who had avoided infection.

“Importantly, people who recover from SARS-CoV-2 infection and then get vaccinated are more protected than people who are unvaccinated,” according to a press release from the National Institutes of Health, which cofunded the study.

The study authors explained that T cells are a critical component of the response to SARS-CoV-2, which is why they sought to better understand those cells’ kinetics after infection and vaccination.

“Using ‘spheromer’ peptide-MHC multimer reagents, we analyzed healthy subjects receiving two doses of the Pfizer/BioNTech BNT162b2 vaccine,” the researchers explained. “Vaccination resulted in robust Spike-specific T cell responses for the dominant CD4+ (HLA-DRB1*15:01/S191) and CD8+ (HLA-A*02/S691) T cell epitopes. Antigen-specific CD4+ and CD8+ T cell responses were asynchronous, with the peak CD4+ T cell responses occurring one week post the second vaccination (boost), whereas CD8+ T cells peaked two weeks later. These peripheral T cell responses were elevated compared to COVID-19 patients.”

In addition, the authors said they determined that prior SARS-CoV-2 infection resulted in decreased CD8+ T-cell activation and expansion, suggesting that “prior infection can influence the T cell response to vaccination.”

For the study, the team analyzed 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.

The results indicated that vaccine recipients who had never been infected with SARS-CoV-2 had robust CD4+ and CD8+ T-cell responses to the virus’ spike protein. T cells also produced multiple types of cytokines that play a key role in fighting pathogens.

Those 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. Moreover, 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,” according to the press release.

Damage to the CD8+ T-cell response appears to be similar to the effects of other viruses such as hepatitis C or HIV, which have longer-term effects on the immune system, according to the authors. They called for the development of vaccination strategies to specifically boost antiviral CD8+ T-cell responses in those previously infected with SARS-CoV-2.

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