Researchers in the United States have conducted a study showing the efficacy of the Moderna and Pfizer-BioNTech vaccines at eliciting a robust T cell response against variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the agent that causes coronavirus disease 2019 (COVID-19).
The team – from Gladstone Institute of Virology in San Francisco and the University of California – also provided evidence that individuals who receive one vaccine dose after having recovered from SARS-CoV-2 infection may not require a second dose.
Furthermore, Nadia Roan and colleagues showed that in previously infected individuals, vaccination might induce more persistent homing of SARS-CoV-2-specific T cells to the respiratory tract than in previously uninfected individuals.
“We find a reassuringly unaltered T cell response against the variants, and a striking impact of prior infection on qualitative features of T cells elicited by vaccination,” writes the team.
A pre-print version of the research paper is available on the bioRxiv* server, while the article undergoes peer review.
Concerns about vaccine efficacy against variants
Since the COVID-19 outbreak first began in late December 2019, intense efforts to develop and clinically test vaccines against SARS-CoV-2 quickly resulted in the emergency use authorization of several mRNA-based vaccines.
Although the Pfizer-BioNTech and Moderna vaccines have proved highly effective at protecting against SARS-CoV-2 infection, concerns have arisen regarding the extent to which they can protect against the new variants that are now quickly spreading across the globe.
The antibodies generated following vaccination generally remain as potent against the B.1.1.7 variant that emerged in the UK as they are against the ancestral strain of SARS-CoV-2. However, studies have also shown the antibodies to be less effective against the B.1.351 lineage that emerged in South Africa and the P.1 variant that emerged in Brazil.
It is also not clear how booster doses and prior infection might influence the vaccine-elicited immunity.
T cell-mediated immunity seems to be less prone to evasion
Reassuringly, early studies have suggested that T cell-mediated immunity appears to be less prone to evasion by the variants.
“The relative resistance of T cells against SARS-CoV-2 immune evasion is important in light of the critical role these immune effectors play during COVID-19,” says Roan and colleagues. “T cell numbers display a strong, inverse association with disease severity and the frequency of SARS-CoV-2-specific T cells predicts recovery from severe disease.”
T cells may also be the key to long-term immune memory due to their ability to persist for decades, adds the team.
Furthermore, studies of the antibody and B cell response to infection suggest that for COVID-19 convalescents, one dose of an mRNA vaccine is beneficial, but that a second booster jab is not necessary.
However, “how this translates in the context of vaccine-elicited T cell immunity is not clear,” says Roan and colleagues.
What did the researchers do?
The team conducted a longitudinal study of eight mRNA-vaccinated individuals, four of whom had recovered from COVID-19 and four of whom were infection-naïve. The researchers conducted a T-cell centric CyTOF (cytometry by time-of-flight) analysis to phenotype participants’ SARS-CoV-2-specific T cells.
Three of the participants had received the Moderna mRNA-1273 vaccine, and the remaining five had received the Pfizer-BioNTech BNT162b2 vaccine.
For each of the 24 samples obtained, the researchers assessed phenotype and effector function of T cells responding to the spike protein of the original SARS-CoV-2 strain and the spikes of the B.1.1.7 (UK) and B.1.351 (South Africa) variants.
The spike protein is the main structure the virus uses to infect host cells and the primary target of neutralizing antibodies following vaccination.
What did they find?
Vaccination-elicited T cells responded similarly to spike epitopes from the ancestral strain and the variants. The phenotypic features of these cells were identical across the different strains.
“That both the quantity and quality of T cell responses is maintained against the variants may provide an explanation for the real-world efficacy of the vaccines against variants,” says the team.
Among the infection-naïve individuals, a second dose boosted the quantity, although not the quality of the spike-specific responses.
The researchers say this highlights the importance of ensuring a second dose is administered to infection-naïve individuals.
Among the convalescent participants, however, there was again no evidence of phenotypic changes in the spike-specific T cells following a second dose, but there was also no evidence of boosted T cell numbers.
“Our results suggest that a second SARS-CoV-2 vaccine dose in individuals who have recovered from COVID-19 may provide less benefit than in individuals who have not previously been exposed to SARS-CoV-2,” says Roen and colleagues.
Differences in phenotypes between convalescent versus infection-naïve vaccinees
The researchers say that one of the most striking findings was the remarkably distinct phenotypes of the spike-specific T cells from convalescent vaccinees versus infection-naïve vaccinees.
The spike-specific CD4+ T cells from the convalescent individuals exhibited features indicating the increased potential for long-term persistence, including the elevated expression of CD127 – a marker of long-lived memory T cells.
Compared with infection-naïve vaccinees, CD4+ T cells from the nasopharynx of the upper respiratory tract in convalescent individuals also expressed multiple tissue-homing receptors.
What are the implications of the study?
“All together, these results imply that compared to infection-naïve individuals, convalescents’ spike-specific CD4+ T cells may be superior in surviving and migrating to the respiratory tract,” write the researchers.
Referring to the findings overall, the team says, “these results provide reassurance that vaccine-elicited T cells respond robustly to the B.1.1.7 and B.1.351 variants, confirm that convalescents may not need a second vaccine dose, and suggest that vaccinated convalescents may have more persistent nasopharynx-homing SARS-CoV-2- specific T cells compared to their infection-naïve counterparts.”
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.