Ethnic Comparisons of Spike-Specific CD4+ T Cells, Serological Responses, and Neutralizing Antibody Titers Against SARS-CoV-2 Variants

Background/Objectives: To evaluate how immune responses compare among ethnic groups approximately 2 years after receiving a third dose of COVID-19 vaccine (BNT162b2, mRNA-1273, ChAdOx1or BBIBP-CorV), we tested T cell responses and Spike-specific RBD-antibody titer, and neutralized antibody titer lev...

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Main Authors: Fani Pantouli, Vanessa Silva-Moraes, Ted M. Ross
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Vaccines
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Online Access:https://www.mdpi.com/2076-393X/13/6/607
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author Fani Pantouli
Vanessa Silva-Moraes
Ted M. Ross
author_facet Fani Pantouli
Vanessa Silva-Moraes
Ted M. Ross
author_sort Fani Pantouli
collection DOAJ
description Background/Objectives: To evaluate how immune responses compare among ethnic groups approximately 2 years after receiving a third dose of COVID-19 vaccine (BNT162b2, mRNA-1273, ChAdOx1or BBIBP-CorV), we tested T cell responses and Spike-specific RBD-antibody titer, and neutralized antibody titer levels utilizing Spectral Flow cytometry, ELISA, and SARS-CoV-2 pseudotyped-based neutralization assays, respectively. Methods: Forty-four individuals from January–December 2023 were identified within the cohort and were classified into different ethnic backgrounds; Black (N = 13), Asian (N = 14), Caucasian (N = 17). We recognize that the “Asian” group includes diverse subpopulations with distinct genetic and environmental backgrounds, which could not be further stratified due to sample-size limitations. Spike-specific AIM+, CD4+, and CD8+ T cell responses were assessed and evaluated against SARS-CoV-2 variants, including the ancestral Wuhan, Delta, and multiple Omicron subvariants (B1.1529, BA2.86, BA.4/5, and XBB.1). Alongside we tested the RBD-IgG and neutralizing antibody titers against the ancestral Wuhan. Spearman’s correlation analysis was utilized to determine corelative relationships among the AIM+ and CD4+ T cell responses, as well as the RBD-IgG and neutralizing antibody titers. Results: Our results show robust and comparable RBD-IgG and neutralizing antibody titers across all groups, with a significant positive correlation between these two measurements. Significant differences were observed in T-cell activation, with Asian participants exhibiting lower frequencies of Spike-specific CD4+ T cells against SARS-CoV-2 Omicron subvariants and higher frequencies of cytokine-producing CD4+ T cells (TNF-α, IFN-γ, and IL-2) as compared to the Caucasian group. Breakthrough infection status was not fully controlled and may influence these findings. Conclusion: Despite a small sample size and potential confounding by natural infections within our long-time-span sampling, our data suggest persistent cellular and humoral immunity 2 years after vaccination across ethnicities, with notable differences in T cell activation and cytokine profile. These preliminary observations highlight the need for larger, more detailed studies that consider intra-ethnic diversity and hybrid immunity to better understand ethnic differences in COVID-19 vaccine responses.
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spelling doaj-art-fdff868572f74040bdba8bf80d7d0bdb2025-08-20T03:32:28ZengMDPI AGVaccines2076-393X2025-06-0113660710.3390/vaccines13060607Ethnic Comparisons of Spike-Specific CD4+ T Cells, Serological Responses, and Neutralizing Antibody Titers Against SARS-CoV-2 VariantsFani Pantouli0Vanessa Silva-Moraes1Ted M. Ross2Florida Research and Innovation Center, Cleveland Clinic, 9801 SW Discovery Way, Port Saint Lucie, FL 34987, USAFlorida Research and Innovation Center, Cleveland Clinic, 9801 SW Discovery Way, Port Saint Lucie, FL 34987, USAFlorida Research and Innovation Center, Cleveland Clinic, 9801 SW Discovery Way, Port Saint Lucie, FL 34987, USABackground/Objectives: To evaluate how immune responses compare among ethnic groups approximately 2 years after receiving a third dose of COVID-19 vaccine (BNT162b2, mRNA-1273, ChAdOx1or BBIBP-CorV), we tested T cell responses and Spike-specific RBD-antibody titer, and neutralized antibody titer levels utilizing Spectral Flow cytometry, ELISA, and SARS-CoV-2 pseudotyped-based neutralization assays, respectively. Methods: Forty-four individuals from January–December 2023 were identified within the cohort and were classified into different ethnic backgrounds; Black (N = 13), Asian (N = 14), Caucasian (N = 17). We recognize that the “Asian” group includes diverse subpopulations with distinct genetic and environmental backgrounds, which could not be further stratified due to sample-size limitations. Spike-specific AIM+, CD4+, and CD8+ T cell responses were assessed and evaluated against SARS-CoV-2 variants, including the ancestral Wuhan, Delta, and multiple Omicron subvariants (B1.1529, BA2.86, BA.4/5, and XBB.1). Alongside we tested the RBD-IgG and neutralizing antibody titers against the ancestral Wuhan. Spearman’s correlation analysis was utilized to determine corelative relationships among the AIM+ and CD4+ T cell responses, as well as the RBD-IgG and neutralizing antibody titers. Results: Our results show robust and comparable RBD-IgG and neutralizing antibody titers across all groups, with a significant positive correlation between these two measurements. Significant differences were observed in T-cell activation, with Asian participants exhibiting lower frequencies of Spike-specific CD4+ T cells against SARS-CoV-2 Omicron subvariants and higher frequencies of cytokine-producing CD4+ T cells (TNF-α, IFN-γ, and IL-2) as compared to the Caucasian group. Breakthrough infection status was not fully controlled and may influence these findings. Conclusion: Despite a small sample size and potential confounding by natural infections within our long-time-span sampling, our data suggest persistent cellular and humoral immunity 2 years after vaccination across ethnicities, with notable differences in T cell activation and cytokine profile. These preliminary observations highlight the need for larger, more detailed studies that consider intra-ethnic diversity and hybrid immunity to better understand ethnic differences in COVID-19 vaccine responses.https://www.mdpi.com/2076-393X/13/6/607COVID-19SARS-CoV-2 variantsspikeethnicityAIM+ CD4+ and CD8+ T cellsactivation markers
spellingShingle Fani Pantouli
Vanessa Silva-Moraes
Ted M. Ross
Ethnic Comparisons of Spike-Specific CD4+ T Cells, Serological Responses, and Neutralizing Antibody Titers Against SARS-CoV-2 Variants
Vaccines
COVID-19
SARS-CoV-2 variants
spike
ethnicity
AIM+ CD4+ and CD8+ T cells
activation markers
title Ethnic Comparisons of Spike-Specific CD4+ T Cells, Serological Responses, and Neutralizing Antibody Titers Against SARS-CoV-2 Variants
title_full Ethnic Comparisons of Spike-Specific CD4+ T Cells, Serological Responses, and Neutralizing Antibody Titers Against SARS-CoV-2 Variants
title_fullStr Ethnic Comparisons of Spike-Specific CD4+ T Cells, Serological Responses, and Neutralizing Antibody Titers Against SARS-CoV-2 Variants
title_full_unstemmed Ethnic Comparisons of Spike-Specific CD4+ T Cells, Serological Responses, and Neutralizing Antibody Titers Against SARS-CoV-2 Variants
title_short Ethnic Comparisons of Spike-Specific CD4+ T Cells, Serological Responses, and Neutralizing Antibody Titers Against SARS-CoV-2 Variants
title_sort ethnic comparisons of spike specific cd4 t cells serological responses and neutralizing antibody titers against sars cov 2 variants
topic COVID-19
SARS-CoV-2 variants
spike
ethnicity
AIM+ CD4+ and CD8+ T cells
activation markers
url https://www.mdpi.com/2076-393X/13/6/607
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AT vanessasilvamoraes ethniccomparisonsofspikespecificcd4tcellsserologicalresponsesandneutralizingantibodytitersagainstsarscov2variants
AT tedmross ethniccomparisonsofspikespecificcd4tcellsserologicalresponsesandneutralizingantibodytitersagainstsarscov2variants