Exploring vaccine-induced cellular immunity against SARS-CoV-2 Omicron variant

In a recent study posted to the medRxiv* preprint server, researchers evaluated the vaccine-induced cellular immune responses cross-reactivity against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant.

Study: Vaccines Elicit Highly Cross-Reactive Cellular Immunity to the SARS-CoV-2 Omicron Variant. Image Credit: haidaralf/ShutterstockStudy: Vaccines Elicit Highly Cross-Reactive Cellular Immunity to the SARS-CoV-2 Omicron Variant. Image Credit: haidaralf/Shutterstock

Background

Studies show that the highly mutated SARS-CoV-2 Omicron (B.1.1.529) variant is associated with widespread coronavirus disease 2019 (COVID-19) transmission and breakthrough infections in double-vaccinated individuals across the globe. Omicron evades a substantial fraction of neutralizing antibody (NAbs) responses elicited by WA1/2020 spike (S) immunogen-targeted vaccines. However, vaccine-induced CD8+ and CD4+ T cell immune responses are likely to play a significant role in protecting from severe COVID-19 disease.

About the study

In the present study, researchers determined CD8+ and CD4+ T cell responses against the SARS-CoV-2 Omicron variant in 51 individuals vaccinated with the messenger ribonucleic acid (mRNA)-based Pfizer and adenovirus vector-based Johnson & Johnson vaccines. 

Samples from subjects who received the Pfizer (n=31) and Johnson & Johnson (n=20) vaccines were collected from the Beth Israel Deaconess Medical Center (BIDMC) specimen biorepository and the COV1001 study, respectively. The participants enrolled in the study after submitting an informed consent. Individuals with a history of SARS-CoV-2 infection, who received other COVID-19 vaccines, and those on immunosuppressive medication were excluded. 

The NAb titers were evaluated at one and eight months after Pfizer and Johnson & Johnson vaccination using a luciferase-based pseudovirus neutralization assay. Subsequently, receptor-binding domain (RBD)-specific binding antibody responses were assessed using enzyme-linked immunosorbent assay (ELISA).

Further, spike (S)-specific cellular immune responses were determined using pooled peptide IFN-γ ELISPOT assays, and S-specific CD8+ and CD4+ T cell responses were assessed using intracellular cytokine staining assays.

Later, Omicron-specific and WA1/2020-specific CD8+ and CD4+ T cell responses of the Johnson & Johnson and Pfizer vaccines were compared using linear regression analysis.

Findings

The results demonstrated a high level of WA1/2020-specific NAb responses at one month following the Pfizer vaccination; however, the Nab response declined after eight months post-vaccination. In contrast, there was a substantially low level of WA1/2020-specific NAb responses at one-month post Johnson & Johnson vaccination; however, the response was more durable and persisted after eight months of vaccination. Both the vaccines elicited minimal cross-reactive Omicron-specific NAb responses, and RBD-specific binding antibody responses also showed minimal cross-reactive Omicron-specific binding antibodies.

The S-specific cellular immune responses from IFN-γ ELISPOT assays showed substantial cross-reactivity to Omicron. The median S-specific IFN-γ CD8+ T cell responses on eight months post-Johnson & Johnson vaccination were 0.062%, 0.061%, and 0.051% against Delta, WA1/2020, and Omicron, respectively.  Further, the median S-specific IFN-γ CD8+ T cell responses at eight months post-Pfizer vaccination were 0.028% and 0.023% against WA1/2020 and Omicron, respectively.

The S-specific IFN-γ CD4+ T cell responses induced by the Johnson & Johnson vaccine was at a median of 0.026%, 0.030%, and 0.029% against WA1/2020, Delta, and Omicron, respectively, and those induced by the Pfizer vaccine was at a median of 0.033% and 0.027% against WA1/2020 and Omicron, respectively.

The S-specific IFN-γ CD8+ and CD4+ T cell central and effector memory subpopulations induced by the Johnson & Johnson vaccine showed extensive cross-reactivity to Delta and Omicron. At eight months post-vaccination, CD8+ central and effector memory responses against WA1/202, Delta, and Omicron were 0.076%, 0.054%, and 0.075% and 0.168%, 0.143%, and 0.146%, respectively. Similarly, CD4+ central and effector memory responses were 0.030%, 0.035%, and 0.038%, and 0.102%, 0.094%, and 0.083%, respectively. 

Additionally, S-specific TNF-α (tumor necrosis factor-alpha) and IL-2 (interleukin 2) secreting CD8+ and CD4+ T cell responses also demonstrated Omicron cross-reactivity.

Omicron-specific CD8+ and CD4+ T cell responses correlated with WA1/2020-specific CD8+ T cell responses for the Johnson & Johnson and Pfizer vaccines at both time points; however, two study participants had undetectable Omicron-specific CD8+ T cell responses after the Pfizer vaccination.

Conclusions

The study findings showed that vaccine-induced cellular immunity had high cross-reactivity against the SARS-CoV-2 Omicron variant. Pfizer and Johnson & Johnson-vaccinated individuals demonstrated long-lasting CD8+ and CD4+ T cell responses with broad cross-reactivity against the Omicron and Delta variants, including in the central and effector memory cellular subpopulations.

The consistency across the viral vector-based Johnson & Johnson and mRNA-based Pfizer vaccines indicated the generalizability of the findings across different vaccine platform technologies. Moreover, the 82-84% median Omicron-specific CD8+ T cell responses were consistent with theoretical predictions based on the Omicron mutations.

The findings were in line with previous studies showing higher cross-reactivity of vaccine-induced cellular immune responses than the humoral immune responses against the SARS-CoV-2 Alpha, Beta, and Gamma variants.

Overall, the findings suggested that despite the substantial reduction in NAb responses and high level of breakthrough infections, the current COVID-19 vaccines may provide significant protection against severe disease with the SARS-CoV-2 Omicron variant.

*Important notice

medRxiv 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.

Journal reference:
Shanet Susan Alex

Written by

Shanet Susan Alex

Shanet Susan Alex, a medical writer, based in Kerala, India, is a Doctor of Pharmacy graduate from Kerala University of Health Sciences. Her academic background is in clinical pharmacy and research, and she is passionate about medical writing. Shanet has published papers in the International Journal of Medical Science and Current Research (IJMSCR), the International Journal of Pharmacy (IJP), and the International Journal of Medical Science and Applied Research (IJMSAR). Apart from work, she enjoys listening to music and watching movies.

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