Whole‐blood cytokine secretion assay as a high‐throughput alternative for assessing the cell‐mediated immunity profile after two doses of an adjuvanted SARS‐CoV‐2 recombinant protein vaccine candidate

Rosa, Stephen C. De; Cohen, Kristen W.; Bonaparte, Matthew; Fu, Bo; Garg, Sanjay; Gérard, Catherine; Goepfert, Paul; Huang, Ying; Larocque, Daniel; McElrath, M. Juliana; Morris, Daryl E.; Most, Robbert van der; Bruyn, Guy de; Pagnon, Anke

doi:10.1002/cti2.1360

Cited by 17 publications

(12 citation statements)

References 45 publications

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“…Therefore, we, similar to several others, refer to this method of whole blood A B cytokine release via mega peptide pools as a T cell test, although we do acknowledge the caveat described above (6,34). T cell responses in previously unexposed individuals developed early after just one vaccination and were maintained after a second dose, a similar finding to that observed by De Rosa et al (35). Interestingly, the amount of IL-2 in individuals with a previous positive PCR result following vaccination was not amplified and was comparable to those with no history of SARS-CoV-2 infection, a finding that was not observed using ELISPOT (36,37).…”

Section: Discussionsupporting

confidence: 74%

“…Positive IL-2 responses were detectable up to 200 d after initial vaccination, and up to 130 d after booster vaccination, in keeping with observations that T cell responses are robust. In SARS-CoV-1 and MERS-CoVinfected individuals, T cell responses were detected several years postinfection (35). It was also reassuring that no significant differences were observed between T cell responses induced by either Pfizer-BioNTech or Oxford/AstraZeneca (ChAdOx1-S) after the initial two doses of vaccines.…”

Section: Discussionmentioning

confidence: 90%

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Longitudinal T Cell Responses against Ancestral, Delta, and Omicron SARS-CoV-2 Variants Determined by Rapid Cytokine Release Assay in Whole Blood

Oliver

Meredith

Smith³

et al. 2022

ImmunoHorizons

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T cell immunity to natural SARS-CoV-2 infection may be more robust and longer lived than Ab responses. Accurate assessment of T cell responses is critical for understanding the magnitude and longevity of immunity across patient cohorts, and against emerging variants. By establishing a simple, accurate, and rapid whole blood test, natural and vaccine-induced SARS-CoV-2 immunity was determined. Cytokine release in whole blood stimulated with peptides specific for SARS-CoV-2 was measured in donors with previous PCR-confirmed infection, suspected infection, or with no exposure history (n 5 128), as well as in donors before and after vaccination (n 5 32). Longitudinal assessment of T cell responses following initial vaccination and booster vaccination was also conducted (n 5 50 and n 5 62, respectively). Cytokines were measured by ELISA and multiplex array. IL-2 and IFN-g were highly elevated in PCRconfirmed donors compared with history-negative controls, with median levels ~33-fold and ~48-fold higher, respectively. Receiver operating curves showed IL-2 as the superior biomarker (area under the curve 5 0.9950). Following vaccination, all donors demonstrated a positive IL-2 response. Median IL-2 levels increased ~32-fold from prevaccination to postvaccination in uninfected individuals. Longitudinal assessment revealed that T cell responses were stable up to 6 mo postvaccination. No significant differences in cytokine production were observed between stimulations with Wuhan, Delta, or Omicron peptides. This rapid, whole blood-based test can be used to make comparable longitudinal assessments of vaccine-induced T cell immunity across multiple cohorts and against variants of concern, thus aiding decisions on public health policies. ImmunoHorizons, 2022, 6: 398-407.

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Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 90%

Longitudinal T Cell Responses against Ancestral, Delta, and Omicron SARS-CoV-2 Variants Determined by Rapid Cytokine Release Assay in Whole Blood

Oliver

Meredith

Smith³

et al. 2022

ImmunoHorizons

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“…Extremely useful future implications of our genetic analyses can also be directed to dissect the molecular mechanisms underlying the individual humoral and cell-mediated variability to the vaccine(s) by in vitro dedicated experiments in relevant cell models. As recently reported, whole blood cultures from subjects after a single dose of anti-SARS-CoV-2 vaccine or after two doses of an adjuvanted SARS-CoV-2 recombinant protein also produced different cytokine secretion profiles ( Lineburg et al, 2021 ; De Rosa et al, 2022 ). This paves the way to design candidate genomic screening and personalized timing to optimize dose administration in any vaccination program.…”

Section: Discussionsupporting

confidence: 53%

Host genetics impact on SARS-CoV-2 vaccine-induced immunoglobulin levels and dynamics: The role of TP53, ABO, APOE, ACE2, HLA-A, and CRP genes

et al. 2022

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Background: Development and worldwide availability of safe and effective vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to fight severe symptoms of coronavirus disease 2019 (COVID-19) and block the pandemic have been a great achievement and stimulated researchers on understanding the efficacy and duration of different vaccine types.Methods: We investigated the levels of anti-SARS-CoV-2 antibodies (IgG) and neutralizing antibodies (NAbs) in 195 healthy adult subjects belonging to the staff of the University-Hospital of Ferrara (Italy) starting from 15 days up to 190 days (about 6 months) after the second dose of the BNT162b2 (Pfizer–BioNTech) mRNA-based vaccine (n = 128) or ChAdOx1 (AstraZeneca) adenovirus-based vaccine (n = 67) using a combined approach of serological and genomics investigations.Results: A strong correlation between IgG and NAb levels was detected during the 190 days of follow-up (r2 = 0.807; p < 0.0001) and was confirmed during the first 90 days (T1) after vaccination (r2 = 0.789; p = 0.0001) and 91–190 days (T2) after vaccination (r2 = 0.764; p = 0.0001) for both vaccine types (r2 = 0.842; p = 0.0001 and r2 = 0.780; p = 0.0001 for mRNA- and adenovirus-based vaccine, respectively). In addition to age (p < 0.01), sex (p = 0.03), and type of vaccine (p < 0.0001), which partially accounted for the remarkable individual differences observed in the antibody levels and dynamics, interesting genetic determinants appeared as significant modifiers of both IgG and NAb responses among the selected genes investigated (TP53, rs1042522; APOE, rs7412/rs429358; ABO, rs657152; ACE2, rs2285666; HLA-A rs2571381/rs2499; CRP, rs2808635/rs876538; LZTFL1, rs35044562; OAS3, rs10735079; SLC6A20, rs11385942; CFH, rs1061170; and ACE1, ins/del, rs4646994). In detail, regression analysis and mean antibody level comparison yielded appreciable differences after genotype stratification (P1 and P2, respectively, for IgG and NAb distribution) in the whole cohort and/or in the mRNA-based vaccine in the following genes: TP53, rs1042522 (P1 = 0.03; P2 = 0.04); ABO, rs657152 (P1 = 0.01; P2 = 0.03); APOE, rs7412/rs429358 (P1 = 0.0018; P2 = 0.0002); ACE2, rs2285666 (P1 = 0.014; P2 = 0.009); HLA-A, rs2571381/rs2499 (P1 = 0.02; P2 = 0.03); and CRP, rs2808635/rs876538 (P1 = 0.01 and P2 = 0.09).Conclusion: High- or low-responsive subjects can be identified among healthy adult vaccinated subjects after targeted genetic screening. This suggests that favorable genetic backgrounds may support the progression of an effective vaccine-induced immune response, though no definite conclusions can be drawn on the real effectiveness ascribed to a specific vaccine or to the different extent of a genotype-driven humoral response. The interplay between data from the polygenic predictive markers and serological screening stratified by demogeographic information can help to recognize the individual humoral response, accounting for ethnic and geographical differences, in both COVID-19 and anti-SARS-CoV-2 vaccinations.

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“…No eOD-GT8-specific CD8 T cell responses were induced, consistent with other clinical studies of adjuvanted recombinant protein vaccines (Fig. 1D) (44)(45)(46)(47). In contrast, we observed induction of LumSyn-specific CD8 T cells among vaccine, but not placebo, recipients.…”

Section: Lumsyn-specific Cd8 T Cells Were Detected Among About Half O...supporting

confidence: 91%

A first-in-human germline-targeting HIV nanoparticle vaccine induced broad and publicly targeted helper T cell responses

et al. 2023

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The engineered outer domain germline targeting version 8 (eOD-GT8) 60-mer nanoparticle was designed to prime VRC01-class HIV-specific B cells that would need to be matured, through additional heterologous immunizations, into B cells that are able to produce broadly neutralizing antibodies. CD4 T cell help will be critical for the development of such high-affinity neutralizing antibody responses. Thus, we assessed the induction and epitope specificities of the vaccine-specific T cells from the IAVI G001 phase 1 clinical trial that tested immunization with eOD-GT8 60-mer adjuvanted with AS01 B . Robust polyfunctional CD4 T cells specific for eOD-GT8 and the lumazine synthase (LumSyn) component of eOD-GT8 60-mer were induced after two vaccinations with either the 20- or 100-microgram dose. Antigen-specific CD4 T helper responses to eOD-GT8 and LumSyn were observed in 84 and 93% of vaccine recipients, respectively. CD4 helper T cell epitope “hotspots” preferentially targeted across participants were identified within both the eOD-GT8 and LumSyn proteins. CD4 T cell responses specific to one of these three LumSyn epitope hotspots were observed in 85% of vaccine recipients. Last, we found that induction of vaccine-specific peripheral CD4 T cells correlated with expansion of eOD-GT8–specific memory B cells. Our findings demonstrate strong human CD4 T cell responses to an HIV vaccine candidate priming immunogen and identify immunodominant CD4 T cell epitopes that might improve human immune responses either to heterologous boost immunogens after this prime vaccination or to other human vaccine immunogens.

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Whole‐blood cytokine secretion assay as a high‐throughput alternative for assessing the cell‐mediated immunity profile after two doses of an adjuvanted SARS‐CoV‐2 recombinant protein vaccine candidate

Cited by 17 publications

References 45 publications

Longitudinal T Cell Responses against Ancestral, Delta, and Omicron SARS-CoV-2 Variants Determined by Rapid Cytokine Release Assay in Whole Blood

Longitudinal T Cell Responses against Ancestral, Delta, and Omicron SARS-CoV-2 Variants Determined by Rapid Cytokine Release Assay in Whole Blood

Host genetics impact on SARS-CoV-2 vaccine-induced immunoglobulin levels and dynamics: The role of TP53, ABO, APOE, ACE2, HLA-A, and CRP genes

A first-in-human germline-targeting HIV nanoparticle vaccine induced broad and publicly targeted helper T cell responses

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