T-cell responses induced by SARS-CoV-2 index-virus nanoparticle protein vaccine to the ancestral and omicron variants 6 months following primary vaccination
Abstract Background The SARS-CoV-2 index-virus nanoparticle protein vaccine (NVX-CoV2373) induces humoral and cell-mediated immune responses that protect against severe COVID-19, including from SARS-CoV-2 variants. Limited information exists on NVX-CoV2373–induced cell-mediated immune responses to a...
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Nature Portfolio
2025-06-01
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| Series: | Communications Medicine |
| Online Access: | https://doi.org/10.1038/s43856-025-00941-4 |
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| author | William C. McMahon Gaurav Kwatra Marta C. Nunes Alane Izu Anthonet L. Koen Johann Greffrath Sharon Shalekoff Caroline T. Tiemessen Vivek Shinde Chijioke Bennett Shabir A. Madhi |
| author_facet | William C. McMahon Gaurav Kwatra Marta C. Nunes Alane Izu Anthonet L. Koen Johann Greffrath Sharon Shalekoff Caroline T. Tiemessen Vivek Shinde Chijioke Bennett Shabir A. Madhi |
| author_sort | William C. McMahon |
| collection | DOAJ |
| description | Abstract Background The SARS-CoV-2 index-virus nanoparticle protein vaccine (NVX-CoV2373) induces humoral and cell-mediated immune responses that protect against severe COVID-19, including from SARS-CoV-2 variants. Limited information exists on NVX-CoV2373–induced cell-mediated immune responses to ancestral SARS-CoV-2 and the Omicron variant following a homologous booster (third dose), and on T-cell responses following a booster dose compared to a single dose. Methods T-cell responses were investigated in participants from a randomised, placebo-controlled, phase 2A/2B trial of NVX-CoV2373 in South Africa, who had a blinded crossover at 6 months post-enrolment. Peripheral blood mononuclear cells were available for 34 participants, 7 days post-vaccination with one NVX-CoV2373 dose (n = 17) or a homologous booster (n = 17). T-cell responses to the full-length spike (FLS) glycoprotein of ancestral Wuhan-Hu-1 SARS-CoV-2 and mutated spike protein regions found in Omicron (BA.4/BA.5) were characterised by intracellular cytokine staining. Results Here we show that FLS-specific T-cell responses are similar between single-dose and booster-dose recipients (CD4+: p = 0.871; CD8+: p = 0.491) and are predominantly monofunctional (IFN-γ or TNF-α). A third NVX-CoV2373 dose increases the FLS-specific polyfunctional cytokine production profile of CD4+ T cells compared with after a single dose (p = 0.045), whereas CD8+ T cells remain unaffected (p = 0.462). Only CD4+ T cells exhibit reduced reactivity to Omicron compared with ancestral SARS-CoV-2 in single-dose (p = 0.010) and in booster-dose recipients (p = 0.028). Conclusions NVX-CoV2373–induced T-cell responses to ancestral SARS-CoV-2 are comparable following vaccination with a single dose compared with a third dose administered 6 months after the second dose. Our findings suggest that an NVX-CoV2373 booster dose does not enhance T-cell immunity. Furthermore, NVX-CoV2373 vaccination induces greater T-cell response magnitudes to ancestral SARS-CoV-2, from which the vaccine is derived, compared with the Omicron variant. |
| format | Article |
| id | doaj-art-408866f445d840cba42966f2dbc6589d |
| institution | DOAJ |
| issn | 2730-664X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Medicine |
| spelling | doaj-art-408866f445d840cba42966f2dbc6589d2025-08-20T03:21:03ZengNature PortfolioCommunications Medicine2730-664X2025-06-015111010.1038/s43856-025-00941-4T-cell responses induced by SARS-CoV-2 index-virus nanoparticle protein vaccine to the ancestral and omicron variants 6 months following primary vaccinationWilliam C. McMahon0Gaurav Kwatra1Marta C. Nunes2Alane Izu3Anthonet L. Koen4Johann Greffrath5Sharon Shalekoff6Caroline T. Tiemessen7Vivek Shinde8Chijioke Bennett9Shabir A. Madhi10South African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the WitwatersrandSouth African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the WitwatersrandSouth African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the WitwatersrandSouth African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the WitwatersrandSouth African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the WitwatersrandSouth African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the WitwatersrandCentre for HIV and STIs, National Institute for Communicable Diseases, a division of the National Health Laboratory ServiceCentre for HIV and STIs, National Institute for Communicable Diseases, a division of the National Health Laboratory ServiceNovavax Inc.Novavax Inc.South African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the WitwatersrandAbstract Background The SARS-CoV-2 index-virus nanoparticle protein vaccine (NVX-CoV2373) induces humoral and cell-mediated immune responses that protect against severe COVID-19, including from SARS-CoV-2 variants. Limited information exists on NVX-CoV2373–induced cell-mediated immune responses to ancestral SARS-CoV-2 and the Omicron variant following a homologous booster (third dose), and on T-cell responses following a booster dose compared to a single dose. Methods T-cell responses were investigated in participants from a randomised, placebo-controlled, phase 2A/2B trial of NVX-CoV2373 in South Africa, who had a blinded crossover at 6 months post-enrolment. Peripheral blood mononuclear cells were available for 34 participants, 7 days post-vaccination with one NVX-CoV2373 dose (n = 17) or a homologous booster (n = 17). T-cell responses to the full-length spike (FLS) glycoprotein of ancestral Wuhan-Hu-1 SARS-CoV-2 and mutated spike protein regions found in Omicron (BA.4/BA.5) were characterised by intracellular cytokine staining. Results Here we show that FLS-specific T-cell responses are similar between single-dose and booster-dose recipients (CD4+: p = 0.871; CD8+: p = 0.491) and are predominantly monofunctional (IFN-γ or TNF-α). A third NVX-CoV2373 dose increases the FLS-specific polyfunctional cytokine production profile of CD4+ T cells compared with after a single dose (p = 0.045), whereas CD8+ T cells remain unaffected (p = 0.462). Only CD4+ T cells exhibit reduced reactivity to Omicron compared with ancestral SARS-CoV-2 in single-dose (p = 0.010) and in booster-dose recipients (p = 0.028). Conclusions NVX-CoV2373–induced T-cell responses to ancestral SARS-CoV-2 are comparable following vaccination with a single dose compared with a third dose administered 6 months after the second dose. Our findings suggest that an NVX-CoV2373 booster dose does not enhance T-cell immunity. Furthermore, NVX-CoV2373 vaccination induces greater T-cell response magnitudes to ancestral SARS-CoV-2, from which the vaccine is derived, compared with the Omicron variant.https://doi.org/10.1038/s43856-025-00941-4 |
| spellingShingle | William C. McMahon Gaurav Kwatra Marta C. Nunes Alane Izu Anthonet L. Koen Johann Greffrath Sharon Shalekoff Caroline T. Tiemessen Vivek Shinde Chijioke Bennett Shabir A. Madhi T-cell responses induced by SARS-CoV-2 index-virus nanoparticle protein vaccine to the ancestral and omicron variants 6 months following primary vaccination Communications Medicine |
| title | T-cell responses induced by SARS-CoV-2 index-virus nanoparticle protein vaccine to the ancestral and omicron variants 6 months following primary vaccination |
| title_full | T-cell responses induced by SARS-CoV-2 index-virus nanoparticle protein vaccine to the ancestral and omicron variants 6 months following primary vaccination |
| title_fullStr | T-cell responses induced by SARS-CoV-2 index-virus nanoparticle protein vaccine to the ancestral and omicron variants 6 months following primary vaccination |
| title_full_unstemmed | T-cell responses induced by SARS-CoV-2 index-virus nanoparticle protein vaccine to the ancestral and omicron variants 6 months following primary vaccination |
| title_short | T-cell responses induced by SARS-CoV-2 index-virus nanoparticle protein vaccine to the ancestral and omicron variants 6 months following primary vaccination |
| title_sort | t cell responses induced by sars cov 2 index virus nanoparticle protein vaccine to the ancestral and omicron variants 6 months following primary vaccination |
| url | https://doi.org/10.1038/s43856-025-00941-4 |
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