Study explores omicron-reactive T- and B- cell responses in COVID-19 vaccine recipients

The rapid spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron variant (B.1.1.529) is a major concern, even among vaccinated individuals.

This has led scientists to worry about the possibility of immune escape.

A new study has been published in Science Immunology that analyzes neutralizing antibodies and T-cell responses targeting the SARS-CoV-2 D614G (wildtype, WT), as well as some variants of concern (VOC), including B.1.351 (Beta), B.1.617.2 (Delta), and B.1.1.529 (Omicron).

Background

The Omicron variant is characterized by a high number of mutations in the spike (S) protein that has immune evasive potential. These mutations include alterations in the receptor-binding domain (RBD), the main target of neutralizing antibodies (nAbs) responsible for host cell entry. Currently, scientists are trying to better understand the Omicron disease severity profile, and how severity is impacted by vaccination and pre-existing immunity.

Currently, nAbs are the main correlate of protection against severe coronavirus disease 2019 (COVID-19). It is more difficult to determine the relative contribution of virus-specific T-cells, which clear infected cells and help in limiting pathogenicity. Previous research has shown that VOC S proteins are equally recognized by S-specific T-cells induced following vaccination with mRNA and adenovirus-based vaccines. Similar results have been derived in more recent studies on T-cell recognition of the Omicron VOC.

Five vaccines have been authorized for use in Europe by the European Medicines Agency (EMA), all of which use the SARS-CoV-2 S protein of the ancestral strain as a template for design. The efficacy of vaccines varies and is affected by the emergence of novel variants. The clinical efficacy and protection against Omicron remain to be determined.

A new study

In the current study, scientists used a cohort of 60 health care workers (HCWs) to study humoral and cellular immune responses early and late post-vaccination. The late follow-up period was up to six months and the vaccines considered were the ChAdOx-1, S, Ad26.COV2.S, mRNA-1273, and BNT162b2. Researchers performed in-depth analyses of the cross-reactivity of nAbs and T-cells. Besides the D614G (wildtype, WT), they also considered the B.1.351 (Beta), B.1.617.2 (Delta), and B.1.1.529 (Omicron) variants. The cross-recognition of variants by nAbs and T-cells after booster vaccination was also studied.

Findings

Scientists demonstrated the resistance of the Omicron variant to nAbs induced by mRNA-based or adenovirus vector-based vaccines. Compared to wild-type SARS-CoV-2, Omicron neutralizing titers were observed to decrease by up to 30-fold. It was found that T-cell responses were not affected significantly by mutations in the Omicron spike protein. An important observation was that a single BNT162b2 booster immunization resulted in a significant rise in Omicron-specific neutralization after priming with either the Ad26.COV2.S or the mRNA-1273 vaccine, in the short term.

Scientists stated that cross-recognition of the different variants by CD4+ and CD8+ T-cells was maintained after booster vaccination. Further, they also observed that the neutralization of Omicron was semi-restored without cross-reactive nAbs, prior to boosting.

Transient but high levels of SARS-CoV-2 specific binding antibodies were observed after mRNA-based vaccination. Researchers also observed that Ad26.COV2.S vaccination led to antibody responses which showed minimal waning at six months, a result corroborated by another independently conducted study. This finding suggested that upon vaccination with Ad26.COV2.S, maturation of B cells occurs without further short-term boosting. Whether antibody responses targeting variants are maintained over longer periods, remains to be studied.

A comprehensive analysis of T-cell responses in vaccinated individuals (early and late) after receiving either the ChAdOx-1 S, Ad26.COV2.S, mRNA-1273, or BNT162b2 vaccine was performed. Durable cellular immune responses were observed, lasting up to six months. This was true for both mRNA-based and adenovirus vector-based vaccines. S-specific CD8+ T-cell responses were obtained in 63% of the vaccine recipients. The number stood at 94% for S-specific CD4+ T-cells. The vaccine-induced T-cells equally recognized the WT, Beta, Delta, and Omicron variants.

Limitations

The sample size (for in-depth T cell profiling) was small, i.e., 15 donors per vaccination regimen. Further, the lower levels of CD8+ T-cells were most likely driven by the use of 15-mer peptides. Additional studies with smaller peptides (8- to 10-nucleotide oligomers) should be carried out to study VOC cross-reactive CD8+ T cell responses. Next, the time series of the data post the booster vaccination is limited and the longevity of the induced immune responses is yet to be determined.

In terms of demographics, the study could have been more balanced, as the current study was skewed towards healthy young-adult participants.

Concluding remarks

This study showed that vaccinated individuals retain T-cell immunity to the Omicron variant. The results imply that immediate booster campaigns should be launched to protect more individuals.

Scientists also stated that variant-specific booster vaccines may be required to optimally skew the immune responses toward novel emerging viruses and, thereby, help to contain the pandemic.

Written by

Dr. Priyom Bose

Priyom holds a Ph.D. in Plant Biology and Biotechnology from the University of Madras, India. She is an active researcher and an experienced science writer. Priyom has also co-authored several original research articles that have been published in reputed peer-reviewed journals. She is also an avid reader and an amateur photographer.