tetano
Editor, Senior Moderator
J Infect Dis
. 2025 May 20:jiaf246.
doi: 10.1093/infdis/jiaf246. Online ahead of print. Hybrid B- and T-Cell Immunity Associates With Protection Against Breakthrough Infection After Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination in Avon Longitudinal Study of Parents and Children (ALSPAC) Participants
Holly E Baum[SUP] 1 2 [/SUP], Marianna Santopaolo[SUP] 1 [/SUP], Ore Francis[SUP] 1 3 [/SUP], Emily J Milodowski[SUP] 3 [/SUP], Katrina Entwistle[SUP] 3 [/SUP], Elizabeth Oliver[SUP] 1 2 [/SUP], Benjamin Hitchings[SUP] 1 2 [/SUP], Divya Diamond[SUP] 1 [/SUP], Amy C Thomas[SUP] 4 [/SUP], Ruth E Mitchell[SUP] 4 [/SUP], Milla Kibble[SUP] 4 5 6 [/SUP], Kapil Gupta[SUP] 7 [/SUP], Natalie Di Bartolo[SUP] 7 [/SUP], Paul Klenerman[SUP] 8 [/SUP], Anthony Brown[SUP] 9 [/SUP], Begonia Morales-Aza[SUP] 1 2 [/SUP], Jennifer Oliver[SUP] 2 4 [/SUP], Imre Berger[SUP] 7 [/SUP], Ash M Toye[SUP] 7 [/SUP], Adam Finn[SUP] 1 2 4 10 [/SUP], Anu Goenka[SUP] 1 2 4 10 [/SUP], Andrew D Davidson[SUP] 1 [/SUP], Susan Ring[SUP] 4 11 [/SUP], Lynn Molloy[SUP] 4 [/SUP], Melanie Lewcock[SUP] 4 [/SUP], Kate Northstone[SUP] 4 [/SUP], Firona Roth[SUP] 4 [/SUP], Nicholas J Timpson[SUP] 4 11 [/SUP], Linda Wooldridge[SUP] 3 [/SUP], Alice Halliday[SUP] 1 2 [/SUP], Laura Rivino[SUP] 1 [/SUP]
Affiliations
Background: Immunological memory to vaccination and viral infection involves the coordinated action of B and T cells; thus, integrated analysis of these 2 components is critical for understanding their respective contributions to protection against breakthrough infections (BIs) after vaccination.
Methods: We investigated cellular and humoral immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and/or vaccination in 300 adult participants from the Avon Longitudinal Study of Parents and Children (ALSPAC). Participants were grouped by those with (cases) and without (controls) a history of SARS-CoV-2 infection. To provide a quantitative correlate for protection against BI in the 8-month period after the study, Youden index thresholds were calculated for all immune measures analyzed.
Results: The magnitude of antibody and T-cell responses following the second vaccine dose was associated with protection against BI in participants with a history of SARS-CoV-2 infection (cases), but not in infection-naive controls. Over 8 months of follow-up, 2 threshold combinations provided the best performance for protection against BI in cases: (i) anti-spike immunoglobulin G (IgG) (≥666.4 binding antibody units [BAU]/mL) combined with anti-nucleocapsid pan-immunoglobulin (pan-Ig) (≥0.1332 BAU/mL) and (ii) spike 1-specific T cells (≥195.6 spot-forming units/106 peripheral blood mononuclear cells) combined with anti-N pan-Ig (≥0.1332 BAU/mL). Both combinations offered 100% specificity for detecting cases without BI, with sensitivities of 83.3% and 72.2%, respectively.
Conclusions: Collectively, these results suggest that hybrid B- and T-cell immunity offers superior protection from BI after coronavirus disease 2019 (COVID-19) vaccination, and this finding has implications for designing next-generation COVID-19 vaccines that are capable of eliciting immunity to a broader repertoire of SARS-CoV-2 proteins.
Keywords: ALSPAC; SARS-CoV-2; breakthrough infection; hybrid immunity; vaccination.
. 2025 May 20:jiaf246.
doi: 10.1093/infdis/jiaf246. Online ahead of print. Hybrid B- and T-Cell Immunity Associates With Protection Against Breakthrough Infection After Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination in Avon Longitudinal Study of Parents and Children (ALSPAC) Participants
Holly E Baum[SUP] 1 2 [/SUP], Marianna Santopaolo[SUP] 1 [/SUP], Ore Francis[SUP] 1 3 [/SUP], Emily J Milodowski[SUP] 3 [/SUP], Katrina Entwistle[SUP] 3 [/SUP], Elizabeth Oliver[SUP] 1 2 [/SUP], Benjamin Hitchings[SUP] 1 2 [/SUP], Divya Diamond[SUP] 1 [/SUP], Amy C Thomas[SUP] 4 [/SUP], Ruth E Mitchell[SUP] 4 [/SUP], Milla Kibble[SUP] 4 5 6 [/SUP], Kapil Gupta[SUP] 7 [/SUP], Natalie Di Bartolo[SUP] 7 [/SUP], Paul Klenerman[SUP] 8 [/SUP], Anthony Brown[SUP] 9 [/SUP], Begonia Morales-Aza[SUP] 1 2 [/SUP], Jennifer Oliver[SUP] 2 4 [/SUP], Imre Berger[SUP] 7 [/SUP], Ash M Toye[SUP] 7 [/SUP], Adam Finn[SUP] 1 2 4 10 [/SUP], Anu Goenka[SUP] 1 2 4 10 [/SUP], Andrew D Davidson[SUP] 1 [/SUP], Susan Ring[SUP] 4 11 [/SUP], Lynn Molloy[SUP] 4 [/SUP], Melanie Lewcock[SUP] 4 [/SUP], Kate Northstone[SUP] 4 [/SUP], Firona Roth[SUP] 4 [/SUP], Nicholas J Timpson[SUP] 4 11 [/SUP], Linda Wooldridge[SUP] 3 [/SUP], Alice Halliday[SUP] 1 2 [/SUP], Laura Rivino[SUP] 1 [/SUP]
Affiliations
- PMID: 40392230
- DOI: 10.1093/infdis/jiaf246
Background: Immunological memory to vaccination and viral infection involves the coordinated action of B and T cells; thus, integrated analysis of these 2 components is critical for understanding their respective contributions to protection against breakthrough infections (BIs) after vaccination.
Methods: We investigated cellular and humoral immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and/or vaccination in 300 adult participants from the Avon Longitudinal Study of Parents and Children (ALSPAC). Participants were grouped by those with (cases) and without (controls) a history of SARS-CoV-2 infection. To provide a quantitative correlate for protection against BI in the 8-month period after the study, Youden index thresholds were calculated for all immune measures analyzed.
Results: The magnitude of antibody and T-cell responses following the second vaccine dose was associated with protection against BI in participants with a history of SARS-CoV-2 infection (cases), but not in infection-naive controls. Over 8 months of follow-up, 2 threshold combinations provided the best performance for protection against BI in cases: (i) anti-spike immunoglobulin G (IgG) (≥666.4 binding antibody units [BAU]/mL) combined with anti-nucleocapsid pan-immunoglobulin (pan-Ig) (≥0.1332 BAU/mL) and (ii) spike 1-specific T cells (≥195.6 spot-forming units/106 peripheral blood mononuclear cells) combined with anti-N pan-Ig (≥0.1332 BAU/mL). Both combinations offered 100% specificity for detecting cases without BI, with sensitivities of 83.3% and 72.2%, respectively.
Conclusions: Collectively, these results suggest that hybrid B- and T-cell immunity offers superior protection from BI after coronavirus disease 2019 (COVID-19) vaccination, and this finding has implications for designing next-generation COVID-19 vaccines that are capable of eliciting immunity to a broader repertoire of SARS-CoV-2 proteins.
Keywords: ALSPAC; SARS-CoV-2; breakthrough infection; hybrid immunity; vaccination.