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[Preprint]. 2022 Jan 3:2022.01.02.22268634.
doi: 10.1101/2022.01.02.22268634.

Vaccines Elicit Highly Cross-Reactive Cellular Immunity to the SARS-CoV-2 Omicron Variant

Jinyan Liu  1 , Abishek Chandrashekar  1 , Daniel Sellers  1 , Julia Barrett  1 , Michelle Lifton  1 , Katherine McMahan  1 , Michaela Sciacca  1 , Haley VanWyk  1 , Cindy Wu  1 , Jingyou Yu  1 , Ai-Ris Y Collier  1 , Dan H Barouch  1   2
Affiliations

Vaccines Elicit Highly Cross-Reactive Cellular Immunity to the SARS-CoV-2 Omicron Variant

Jinyan Liu et al. medRxiv. .

Update in

Abstract

The highly mutated SARS-CoV-2 Omicron (B.1.1.529) variant has been shown to evade a substantial fraction of neutralizing antibody responses elicited by current vaccines that encode the WA1/2020 Spike immunogen 1 , resulting in increased breakthrough infections and reduced vaccine efficacy. Cellular immune responses, particularly CD8+ T cell responses, are likely critical for protection against severe SARS-CoV-2 disease 2-6 . Here we show that cellular immunity induced by current SARS-CoV-2 vaccines is highly cross-reactive against the SARS-CoV-2 Omicron variant. Individuals who received Ad26.COV2.S or BNT162b2 vaccines demonstrated durable CD8+ and CD4+ T cell responses that showed extensive cross-reactivity against both the Delta and Omicron variants, including in central and effector memory cellular subpopulations. Median Omicron-specific CD8+ T cell responses were 82-84% of WA1/2020-specific CD8+ T cell responses. These data suggest that current vaccines may provide considerable protection against severe disease with the SARS-CoV-2 Omicron variant despite the substantial reduction of neutralizing antibody responses.

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Conflict of interest statement

Conflicts of Interest

DHB is a co-inventor on provisional vaccine patents (63/121,482; 63/133,969; 63/135,182). The authors report no other conflict of interest.

Figures

Extended Data Figure 1.
Extended Data Figure 1.. Cellular immune responses to Omicron by ELISPOT assays.
Spike-specific IFN-γ ELISPOT assays at month 1 and 8 following vaccination with Ad26.COV2.S or BNT162b2. Responses were measured against the SARS-CoV-2 WA1/2020, B.1.617.2 (Delta), and B.1.1.529 (Omicron) variants. Medians (red bars) are depicted and numerically shown.
Extended Data Figure 2.
Extended Data Figure 2.. Cellular immune responses to Omicron by intracellular cytokine staining assays.
Spike-specific IFN-γ, TNF-α, and IL-2 CD8+ and CD4+ T cell responses by intracellular cytokine staining assays at month 8 following vaccination with Ad26.COV2.S. Responses were measured against the SARS-CoV-2 WA1/2020, B.1.617.2 (Delta), and B.1.1.529 (Omicron) variants. Medians (red bars) are depicted and numerically shown.
Figure 1.
Figure 1.. Humoral immune responses to Omicron.
Antibody responses at months 1 and 8 following vaccination with Ad26.COV2.S or BNT162b2. a, Neutralizing antibody (NAb) titers by a luciferase-based pseudovirus neutralization assay. b, Receptor binding domain (RBD)-specific binding antibody titers by ELISA. Responses were measured against the SARS-CoV-2 WA1/2020, B.1.617.2 (Delta), B.1.351 (Beta), and B.1.1.529 (Omicron) variants. Medians (red bars) are depicted and numerically shown.
Figure 1.
Figure 1.. Humoral immune responses to Omicron.
Antibody responses at months 1 and 8 following vaccination with Ad26.COV2.S or BNT162b2. a, Neutralizing antibody (NAb) titers by a luciferase-based pseudovirus neutralization assay. b, Receptor binding domain (RBD)-specific binding antibody titers by ELISA. Responses were measured against the SARS-CoV-2 WA1/2020, B.1.617.2 (Delta), B.1.351 (Beta), and B.1.1.529 (Omicron) variants. Medians (red bars) are depicted and numerically shown.
Figure 2.
Figure 2.. Cellular immune responses to Omicron.
T cell responses at months 1 and 8 following vaccination with Ad26.COV2.S or BNT162b2. Pooled peptide Spike-specific IFN-γ (a) CD8+ T cell responses and (b) CD4+ T cell responses by intracellular cytokine staining assays. Responses were measured against the SARS-CoV-2 WA1/2020, B.1.617.2 (Delta), and B.1.1.529 (Omicron) variants. Medians (red bars) are depicted and numerically shown.
Figure 2.
Figure 2.. Cellular immune responses to Omicron.
T cell responses at months 1 and 8 following vaccination with Ad26.COV2.S or BNT162b2. Pooled peptide Spike-specific IFN-γ (a) CD8+ T cell responses and (b) CD4+ T cell responses by intracellular cytokine staining assays. Responses were measured against the SARS-CoV-2 WA1/2020, B.1.617.2 (Delta), and B.1.1.529 (Omicron) variants. Medians (red bars) are depicted and numerically shown.
Figure 3.
Figure 3.. Correlations of variant- and WA1/2020-specific cellular immune responses.
Correlations of Log Delta- and Omicron-specific to Log WA1/2020-specific (a) CD8+ T cell responses and (b) CD4+ T cell responses by intracellular cytokine staining assays. Lines of best fit by logistic regression are shown.
Figure 3.
Figure 3.. Correlations of variant- and WA1/2020-specific cellular immune responses.
Correlations of Log Delta- and Omicron-specific to Log WA1/2020-specific (a) CD8+ T cell responses and (b) CD4+ T cell responses by intracellular cytokine staining assays. Lines of best fit by logistic regression are shown.
Figure 4.
Figure 4.. Cellular immune memory subpopulations to Omicron.
Pooled peptide Spike-specific IFN-γ CD8+ and CD4+ central memory (CD45RA-CD27+) and effector memory (CD45RA-CD27-) T cell responses by intracellular cytokine staining assays at months 1 and 8 following vaccination with Ad26.COV2.S. Responses were measured against the SARS-CoV-2 WA1/2020, B.1.617.2 (Delta), and B.1.1.529 (Omicron) variants. Medians (red bars) are depicted and numerically shown.
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