We analyzed magnitude and duration of SARS-CoV-2-specific T cell responses in healthy, infection-naïve subjects receiving COVID-19 vaccines. Overlapping peptides spanning the N-terminal spike 1 (S1) ...domain of the spike protein triggered secretion of the T cell-derived cytokine interleukin-2 ex vivo in 94/94 whole blood samples from vaccinated subjects at levels exceeding those recorded in all 45 pre-vaccination samples. S1-specific T cell reactivity was stronger in vaccinated subjects compared with subjects recovering from natural COVID-19 and decayed with an estimated half-life of 134 days in the first six months after the 2nd vaccination. We conclude that COVID-19 vaccination induces robust T cell immunity that subsequently declines.
EudraCT 2021–000349-42.
https://www.clinicaltrialsregister.eu/ctr-search/search?query=2021-000349-42
Abstract
Background
Waning of immunoglobulin G (IgG) antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) complicates the diagnosis of past infection. The durability of ...T-cell memory against SARS-CoV-2 remains unclear, and most current T-cell protocols are unsuited for large-scale automation.
Methods
Whole-blood samples from 31 patients with verified past coronavirus disease 2019 (COVID-19) and 46 controls, of whom 40 received COVID-19 vaccine, were stimulated with peptides spanning the nucleocapsid (NC) or spike 1 (S1) regions of SARS-CoV-2 and analyzed for interferon γ in supernatant plasma. Diagnostic accuracy of these assays was evaluated against serum anti-NC and anti–receptor-binding domain S1-IgG.
Results
Induction of interferon γ in whole blood by NC or S1 peptides diagnosed past COVID-19 with high accuracy (area under the receiver operating characteristic curve, 0.93 and 0.95, respectively). In accordance with previous studies, NC-IgG levels rapidly waned with only 5 of 17 patients (29%) remaining seropositive >180 days after infection. By contrast, NC peptide–induced T-cell memory responses remained in 13 of 17 study participants (76%) >180 days after infection (P = .01 for comparison with NC-IgG; McNemar test). After 2 vaccine doses, all 18 donors exhibited S1-specific T-cell memory.
Conclusions
Cytokine release assays for the monitoring of T-cell memory in whole blood may be useful for evaluating complications following unverified past COVID-19 and for long-term assessment of vaccine-induced T-cell immunity.
Clinical Trials Registration
EudraCT 2021-000349-42.
We developed a simple and sensitive whole-blood stimulation assay to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific T cells in previously infected or vaccinated individuals. Virus-specific T-cell responses persisted significantly longer than SARS-CoV-2–specific immunoglobulin G responses.
Background & Aims
In 2014, the burden of hepatitis C virus (HCV) in Sweden was evaluated, to establish a baseline and inform public health interventions. Considering the changing landscape of HCV ...treatment, prevention, and care, and in light of the COVID‐19 pandemic, this analysis seeks to evaluate Sweden's progress towards the World Health Organization (WHO) elimination targets and identify remaining barriers.
Methods
The data used for modelling HCV transmission and disease burden in Sweden were obtained through literature review, unpublished sources and expert input. A dynamic Markov model was employed to forecast population sizes and incidence of HCV through 2030. Two scenarios (‘2019 Base’ and ‘WHO Targets’) were developed to evaluate Sweden's progress towards HCV elimination.
Results
At the beginning of 2019, there were 29 700 (95% uncertainty interval: 19 300‐33 700) viremic infections in Sweden. Under the base scenario, Sweden would achieve and exceed the WHO targets for diagnosis, treatment and liver‐related death. However, new infections would decrease by less than 10%, relative to 2015. Achieving all WHO targets by 2030 would require (i) expanding harm reduction programmes to reach more than 90% of people who inject drugs (PWID) and (ii) treating 90% of HCV + PWID engaged in harm reduction programmes and ≥7% of PWID not involved in harm reduction programmes, annually by 2025.
Conclusions
It is of utmost importance that Sweden, and all countries, find sustainability in HCV programmes by broadening the setting and base of providers to provide stability and continuity of care during turbulent times.
Waning of IgG antibodies against SARS-CoV-2 complicates diagnosis of past infection. Durability of T cell memory against SARS-CoV-2 remains unclear, and most current T cell protocols are unsuited for ...large-scale automation.
Whole blood samples from 31 patients with verified past COVID-19 and 46 controls, out of which 40 received SARS-CoV-2 vaccine were stimulated with peptides spanning the nucleocapsid (NC) or spike 1 (S1) regions of SARS-CoV-2 and analyzed for interferon-γ (IFN-γ) in supernatant plasma. Diagnostic accuracy of these assays was evaluated against serum anti-NC and anti-receptor-binding domain S1 IgG.
Induction of IFN-γ in whole blood by NC or S1 peptides diagnosed past COVID-19 with high accuracy (AUC=0.93, AUC=0.95, respectively). In accordance with previous studies, NC-IgG levels rapidly waned with only 5/17 patients (29%) remaining seropositive >180 days after infection. By contrast, NC-peptide-induced T cell memory responses remained in 13/17 (76%) subjects >180 days after infection (P=0.012 vs. NC-IgG, McNemar test). After two vaccine doses, 18/18 donors exhibited S1-specific T cell memory.
Cytokine release assays for the monitoring of T cell memory in whole blood may be useful for evaluation of complications following unverified past COVID-19 and for long-term assessment of vaccine-induced T cell immunity.
Despite recombinant interferon-λ 4 (IFN-λ4) demonstrating anti-viral activity in vitro and the ancestral functional gene (IFNL4) being conserved in all other primates, there has been speculation that ...IFN-λ4 may be detrimental in humans. In light of recent rekindled interest in humoral immunity, this study aimed at evaluating the impact of baseline characteristics, including IFNL4, on antibody levels to hepatitis C virus (HCV).
Pretreatment sera from 279 well-characterized North European Caucasians with chronic HCV genotype 2 or 3 infection having undergone liver biopsy were analyzed regarding IFNL4 (rs12979860) and anti-HCV antibody levels using a commercially available assay.
Patients producing IFN-λ4 had higher signal to cut-off (S/CO) anti-HCV antibody ratios as compared with those lacking IFN-λ4 (IFNL4
rs12979860
CT/TT versus CC, p<.0001, Mann-Whitney U-test). Additionally, in univariate analyses S/CO was significantly higher in men than women (p<.001), as well as in patients with absent/mild interface hepatitis (Ishak grade 0-2 versus 3-4, p = .009), and absent/mild steatosis (grade 0-1 versus 2-3, p = .0005). Also, an inverse correlation with HCV RNA level (r
s
= −0.14, p = .02) was noted. In multivariate analysis IFN-λ4, gender, steatosis and viral load remained independently associated.
To our knowledge, this is the first report that demonstrates that the ability to produce IFN-λ4, in addition to male gender, absent/mild steatosis, and lower viral load, augments antibody levels against HCV. This indicates that IFN-λ4 may be associated with T helper cell 2 (Th2) immune skewing, which might have clinical implications beyond HCV infection. ClinicalTrials.gov Identifier: NCT00143000
Background & Aims Single nucleotide polymorphisms (SNPs) associated with IL28B influence the outcome of peginterferon-α/ribavirin therapy of chronic hepatitis C virus (HCV) infection. We analyzed the ...kinetics of HCV RNA during therapy as a function of IL28B SNPs. Methods IL28B SNPs rs8099917, rs12979860, and rs12980275 were genotyped in 242 HCV treatment-naïve Caucasian patients (67% genotype 1, 28% genotype 2 or 3) receiving peginterferon-α2a (180 μg weekly) and ribavirin (1000–1200 mg daily) with serial HCV-RNA quantifications. Associations between IL28B polymorphisms and early viral kinetics were assessed, accounting for relevant covariates. Results In the multivariate analyses for genotype 1 patients, the T allele of rs12979860 (Trs12979860 ) was an independent risk factor for a less pronounced first phase HCV RNA decline (log10 0.89 IU/ml among T carriers vs. 2.06 among others, adjusted p <0.001) and lower rapid (15% vs. 38%, adjusted p = 0.007) and sustained viral response rates (48% vs. 66%, adjusted p <0.001). In univariate analyses, Trs12979860 was also associated with a reduced second phase decline ( p = 0.002), but this association was no longer significant after adjustment for the first phase decline (adjusted p = 0.8). In genotype 2/3 patients, Trs12979860 was associated with a reduced first phase decline (adjusted p = 0.04), but not with a second phase decline. Conclusions Polymorphisms in IL28B are strongly associated with the first phase viral decline during peginterferon-α/ribavirin therapy of chronic HCV infection, irrespective of HCV genotype.
Per- and polyfluoroalkyl substances (PFAS) are widely used, environmentally ubiquitous, and stable chemicals that have been associated with lower vaccine-induced antibody responses in children; ...however, data on adults are limited. The drinking water from one of the two waterworks in Ronneby, Sweden, was heavily contaminated for decades with PFAS from firefighting foams, primarily perfluorohexane sulfonic acid and perfluorooctanesulfonic acid (PFOS). Vaccination against SARS-CoV-2 offered a unique opportunity to investigate antibody responses to primary vaccination in adults who had been exposed to PFAS.
Our objective was to evaluate associations between PFAS, across a wide range of exposure levels, and antibody responses in adults 5 wk and 6 months after a two-dose vaccination regime against SARS-CoV-2.
Adults age 20-60 y from Ronneby (
, median PFOS serum level
, fifth to 95th percentile
) and a group with background exposure (
, median PFOS serum level
) received two doses of the Spikevax (Moderna) mRNA vaccine. The levels of seven PFAS were measured in serum before vaccination. Serum immunoglobulin G antibodies against the SARS-CoV-2 spike antigen (S-Abs) were measured before vaccination and at 5 wk (
) and 6 months (
) after the second vaccine dose. Linear regression analyses were fitted against current, historical, and prenatal exposure to PFAS, adjusting for sex, age, and smoking, excluding individuals with previous SARS-CoV-2-infection.
PFAS exposure, regardless of how it was estimated, was not negatively associated with antibody levels 5 wk current PFOS:
S-Abs/PFOS interquartile range (IQR); 95% confidence interval (CI):
, 7 or 6 months (current PFOS: 3% S-Abs/PFOS IQR; 95% CI:
, 12) after COVID-19 vaccination.
Following a strict study protocol, rigorous study design, and few dropouts, we found no indication that PFAS exposure negatively affected antibody responses to COVID-19 mRNA vaccination for up to 6 months after vaccination. https://doi.org/10.1289/EHP11847.
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