tetano
Editor, Senior Moderator
mBio
. 2023 Sep 1;e0121223.
doi: 10.1128/mbio.01212-23. Online ahead of print. CD4+ and CD8+ T cells and antibodies are associated with protection against Delta vaccine breakthrough infection: a nested case-control study within the PITCH study
Isabel Neale[SUP] 1 2 3 [/SUP], Mohammad Ali[SUP] 1 2 3 [/SUP], Barbara Kronsteiner[SUP] 1 2 [/SUP], Stephanie Longet[SUP] 4 5 [/SUP], Priyanka Abraham[SUP] 1 2 [/SUP], Alexandra S Deeks[SUP] 1 6 [/SUP], Anthony Brown[SUP] 1 [/SUP], Shona C Moore[SUP] 7 [/SUP], Lizzie Stafford[SUP] 5 [/SUP], Susan L Dobson[SUP] 7 [/SUP], Megan Plowright[SUP] 8 9 [/SUP], Thomas A H Newman[SUP] 8 9 [/SUP], Mary Y Wu[SUP] 10 [/SUP]; Crick COVID Immunity Pipeline[SUP] 10 11 [/SUP]; Edward J Carr[SUP] 11 [/SUP], Rupert Beale[SUP] 11 12 [/SUP], Ashley D Otter[SUP] 13 [/SUP], Susan Hopkins[SUP] 14 [/SUP], Victoria Hall[SUP] 14 [/SUP], Adriana Tomic[SUP] 15 16 17 18 [/SUP], Rebecca P Payne[SUP] 19 [/SUP], Eleanor Barnes[SUP] 1 6 20 21 [/SUP], Alex Richter[SUP] 22 23 [/SUP], Christopher J A Duncan[SUP] 19 24 [/SUP], Lance Turtle[SUP] 7 25 [/SUP], Thushan I de Silva[SUP] 8 9 [/SUP], Miles Carroll[SUP] 4 5 [/SUP], Teresa Lambe[SUP] 18 26 [/SUP], Paul Klenerman[SUP] 1 6 20 21 [/SUP], Susanna Dunachie[SUP] 1 2 3 6 [/SUP]; PITCH Consortium
Affiliations
Serological correlates of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection after vaccination ("vaccine breakthrough") have been described. However, T cell correlates of protection against breakthrough are incompletely defined, especially the specific contributions of CD4+ and CD8+ T cells. Here, 279 volunteers in the Protective Immunity from T Cells in Healthcare Workers (PITCH) UK cohort study were enrolled in a nested case-control study. Cases were those who tested SARS-CoV-2 PCR or lateral flow device (LFD) positive after two vaccine doses during the Delta-predominant era (n = 32), while controls were those who did not report a positive test or undergo anti-nucleocapsid immunoglobulin G (IgG) seroconversion during this period (n = 247). Previous SARS-CoV-2 infection prior to vaccination was associated with reduced odds of vaccine breakthrough. Using samples from 28 d after the second vaccine dose, before all breakthroughs occurred, we observed future cases had lower ancestral spike (S)- and receptor binding domain-specific IgG titers and S1- and S2-specific T cell interferon gamma (IFNγ) responses compared with controls, although these differences did not persist when individuals were stratified according to previous infection status before vaccination. In a subset of matched infection-naïve cases and controls, vaccine breakthrough cases had lower CD4+ and CD8+ IFNγ and tumor necrosis factor (TNF) responses to Delta S peptides compared with controls. For CD8+ responses, this difference appeared to be driven by reduced responses to Delta compared with ancestral peptides among cases; this reduced response to Delta peptides was not observed in controls. Our findings support a protective role for T cells against Delta breakthrough infection. IMPORTANCE Defining correlates of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine breakthrough infection informs vaccine policy for booster doses and future vaccine designs. Existing studies demonstrate humoral correlates of protection, but the role of T cells in protection is still unclear. In this study, we explore antibody and T cell immune responses associated with protection against Delta variant vaccine breakthrough infection in a well-characterized cohort of UK Healthcare Workers (HCWs). We demonstrate evidence to support a role for CD4+ and CD8+ T cells as well as antibodies against Delta vaccine breakthrough infection. In addition, our results suggest a potential role for cross-reactive T cells in vaccine breakthrough.
Keywords: COVID vaccine; COVID-19; Delta; SARS-CoV-2; T cells; antibody; immunity; vaccine breakthrough.
. 2023 Sep 1;e0121223.
doi: 10.1128/mbio.01212-23. Online ahead of print. CD4+ and CD8+ T cells and antibodies are associated with protection against Delta vaccine breakthrough infection: a nested case-control study within the PITCH study
Isabel Neale[SUP] 1 2 3 [/SUP], Mohammad Ali[SUP] 1 2 3 [/SUP], Barbara Kronsteiner[SUP] 1 2 [/SUP], Stephanie Longet[SUP] 4 5 [/SUP], Priyanka Abraham[SUP] 1 2 [/SUP], Alexandra S Deeks[SUP] 1 6 [/SUP], Anthony Brown[SUP] 1 [/SUP], Shona C Moore[SUP] 7 [/SUP], Lizzie Stafford[SUP] 5 [/SUP], Susan L Dobson[SUP] 7 [/SUP], Megan Plowright[SUP] 8 9 [/SUP], Thomas A H Newman[SUP] 8 9 [/SUP], Mary Y Wu[SUP] 10 [/SUP]; Crick COVID Immunity Pipeline[SUP] 10 11 [/SUP]; Edward J Carr[SUP] 11 [/SUP], Rupert Beale[SUP] 11 12 [/SUP], Ashley D Otter[SUP] 13 [/SUP], Susan Hopkins[SUP] 14 [/SUP], Victoria Hall[SUP] 14 [/SUP], Adriana Tomic[SUP] 15 16 17 18 [/SUP], Rebecca P Payne[SUP] 19 [/SUP], Eleanor Barnes[SUP] 1 6 20 21 [/SUP], Alex Richter[SUP] 22 23 [/SUP], Christopher J A Duncan[SUP] 19 24 [/SUP], Lance Turtle[SUP] 7 25 [/SUP], Thushan I de Silva[SUP] 8 9 [/SUP], Miles Carroll[SUP] 4 5 [/SUP], Teresa Lambe[SUP] 18 26 [/SUP], Paul Klenerman[SUP] 1 6 20 21 [/SUP], Susanna Dunachie[SUP] 1 2 3 6 [/SUP]; PITCH Consortium
Affiliations
- PMID: 37655880
- DOI: 10.1128/mbio.01212-23
Serological correlates of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection after vaccination ("vaccine breakthrough") have been described. However, T cell correlates of protection against breakthrough are incompletely defined, especially the specific contributions of CD4+ and CD8+ T cells. Here, 279 volunteers in the Protective Immunity from T Cells in Healthcare Workers (PITCH) UK cohort study were enrolled in a nested case-control study. Cases were those who tested SARS-CoV-2 PCR or lateral flow device (LFD) positive after two vaccine doses during the Delta-predominant era (n = 32), while controls were those who did not report a positive test or undergo anti-nucleocapsid immunoglobulin G (IgG) seroconversion during this period (n = 247). Previous SARS-CoV-2 infection prior to vaccination was associated with reduced odds of vaccine breakthrough. Using samples from 28 d after the second vaccine dose, before all breakthroughs occurred, we observed future cases had lower ancestral spike (S)- and receptor binding domain-specific IgG titers and S1- and S2-specific T cell interferon gamma (IFNγ) responses compared with controls, although these differences did not persist when individuals were stratified according to previous infection status before vaccination. In a subset of matched infection-naïve cases and controls, vaccine breakthrough cases had lower CD4+ and CD8+ IFNγ and tumor necrosis factor (TNF) responses to Delta S peptides compared with controls. For CD8+ responses, this difference appeared to be driven by reduced responses to Delta compared with ancestral peptides among cases; this reduced response to Delta peptides was not observed in controls. Our findings support a protective role for T cells against Delta breakthrough infection. IMPORTANCE Defining correlates of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine breakthrough infection informs vaccine policy for booster doses and future vaccine designs. Existing studies demonstrate humoral correlates of protection, but the role of T cells in protection is still unclear. In this study, we explore antibody and T cell immune responses associated with protection against Delta variant vaccine breakthrough infection in a well-characterized cohort of UK Healthcare Workers (HCWs). We demonstrate evidence to support a role for CD4+ and CD8+ T cells as well as antibodies against Delta vaccine breakthrough infection. In addition, our results suggest a potential role for cross-reactive T cells in vaccine breakthrough.
Keywords: COVID vaccine; COVID-19; Delta; SARS-CoV-2; T cells; antibody; immunity; vaccine breakthrough.