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1.
Clin Infect Dis ; 2021 Dec 10.
Article in English | MEDLINE | ID: covidwho-2017796

ABSTRACT

BACKGROUND: We evaluated a standardized interferon-γ (IFN-γ) release assay (IGRA) for detection of T-cell immune response after SARS-CoV-2 infection or vaccination. METHODS: This prospective study included COVID-19 patients with different severity of illness and follow-up (FU), vaccinated subjects, and healthy unvaccinated persons. SARS-CoV-2 T-cell response was measured using a specific quantitative IGRA in whole blood (Euroimmun, Germany) and TrimericS-IgG and neutralizing antibodies with validated serological platforms. Positivity of RT-PCR or vaccination was considered as reference standard. RESULTS: Two hundred and thirty nine individuals were included (152 convalescent, 54 vaccinated and 33 uninfected unvaccinated). Overall sensitivity, specificity, positive (PPV) and negative (NPV) predictive values (95% CI) of the IGRA were 81.1% (74.9%-86%), 90.9% (74.5%-97.6%), 98.2% (94.5%-99.5%), and 43.5% (31.8%-55.9%), respectively. All vaccinated SARS-CoV-2-naïve subjects had positive IGRA at 3 months. In convalescent subjects the magnitude of IFN-γ responses and IGRA accuracy varied according to disease severity and duration of FU, with the best performance in patients with severe COVID-19 at 3-month and the worst in those with mild disease at 12-month. The greatest contribution of IGRA to serological tests was observed in patients with mild disease and long-term FU (incremental difference, 30.4%). CONCLUSION: The IGRA assessed was a reliable method of quantifying T-cell response after SARS-COV-2 infection or vaccination. In convalescent patients the sensitivity is largely dependent on disease severity and time since primary infection. The assay is more likely to add clinical value to serology in patients with mild infections.

2.
Pathog Dis ; 2022.
Article in English | PubMed | ID: covidwho-2017915

ABSTRACT

Effective vaccination is a key element in the exit strategy from the current severe acute respiratory syndrome- CoV coronavirus-2 (SARS-CoV-2) pandemic, and may also offer protection against severe disease from future variants of concern. Here we prospectively monitored T- cell responses over time, using ELISpot interferon-γ (INF-y) release assays, and B- cell responses, using serological tests, after vaccination and booster with BioNTech/Pfizer mRNA (Pfizer) and Janssen vector (Janssen/Johnson & Johnson) vaccines in hospital health care workers. Vaccine recipients were divided into seropositive and seronegative individuals at baseline, in order to determine the effect of natural immunity on vaccine-induced immune kinetics. We found that convalescent individuals mounted higher spike-specific INF-y-secreting T cell responses and B- cell-mediated IgG responses, after receiving the Janssen vaccine or the first dose of the Pfizer vaccine. IgG levels corresponded to the virus neutralisation capacity as measured by VNT assay. At 8 months post vaccination, spike-specific cellular immunity waned to low levels in individuals with or without prior natural immunity, whereas waning of humoral immunity occurred predominantly in naive individuals. The booster shot effectively re-induced both cellular and humoral immune responses. To conclude, our data supports the implemented single-dose mRNA booster strategy employed in the Netherlands. Furthermore, the level of pre-existing natural immunity may be factored into determining the optimal time window between future booster vaccines.

3.
Clin Infect Dis ; 2022 Jan 25.
Article in English | MEDLINE | ID: covidwho-2017819

ABSTRACT

BACKGROUND: An immunodiagnostic assay that sensitively detects a cell-mediated immune response to SARS-CoV-2 is needed for epidemiological investigation and for clinical assessment of T cell-mediated immune response to vaccines, particularly in the context of emerging variants that might escape antibody responses. METHODS: The performance of a whole blood interferon-gamma (IFN-γ) release assay (IGRA) for the detection of SARS-CoV-2 antigen-specific T cells was evaluated in COVID-19 convalescents tested serially up to 10 months post-infection and in healthy blood donors. SARS-CoV-2 IGRA was applied in contacts of households with index cases. Freshly collected blood in the lithium heparin tube was left unstimulated, stimulated with a SARS-CoV-2 peptide pool, and stimulated with mitogen. RESULTS: The overall sensitivity and specificity of IGRA were 84.5% (153/181; 95% confidence interval [CI] 79.0-89.0) and 86.6% (123/142; 95% CI;80.0-91.2), respectively. The sensitivity declined from 100% (16/16; 95% CI 80.6-100) at 0.5-month post-infection to 79.5% (31/39; 95% CI 64.4-89.2) at 10 months post-infection (P<0.01). The IFN-γ response remained relatively robust at 10 months post-infection (3.8 vs. 1.3 IU/mL, respectively). In 14 households, IGRA showed a positivity rate of 100% (12/12) and 65.2% (15/23), and IgG of 50.0% (6/12) and 43.5% (10/23) in index cases and contacts, respectively, exhibiting a difference of +50% (95% CI +25.4-+74.6) and +21.7% (95% CI, +9.23-+42.3), respectively. Either IGRA or IgG was positive in 100% (12/12) of index cases and 73.9% (17/23) of contacts. CONCLUSIONS: The SARS-CoV-2 IGRA is a useful clinical diagnostic tool for assessing cell-mediated immune response to SARS-CoV-2.

4.
Int J Infect Dis ; 2022 Jul 22.
Article in English | MEDLINE | ID: covidwho-2015442

ABSTRACT

OBJECTIVE: Characterization of the SARS-CoV-2-specific T-cell response detected by the QuantiFERON SARS-CoV-2 RUO assay in terms of accuracy and T-cell subsets involved compared to a homemade interferon (IFN)-γ release assay (IGRA). METHODS: We evaluated T-cell response by the standardized QuantiFERON SARS-CoV-2 tubes (Ag1 and Ag2) and a homemade IGRA quantifying IFN-γ response to SARS-CoV-2 spike peptides (homemade-IGRA-SPIKE test). By flow cytometry, we evaluated the T-cell subsets mediating the specific response. RESULTS: We prospectively enrolled 66 individuals: COVID-19 or post-COVID-19 subjects, and NO-COVID-19-vaccinated subjects, including healthy donors and immunocompromised subjects. The standardized kit detected 62.1% (41/66) of T-cell responders. Ag2 tube showed the higher IFN-γ quantitative and qualitative response. Ag1 tube response was mainly mediated by CD4+ T cells; Ag2 tube response was mediated by both CD4+ and CD8+ T cells. The homemade-IGRA-SPIKE test detected a higher number of responders (52/66, 78.8%) than QuantiFERON SARS-CoV-2 assay (p=0.056), and the response was found in both T-cell subsets, although a higher magnitude and response rate was observed in the CD4+ T-cell subset. CONCLUSIONS: QuantiFERON SARS-CoV-2 response is mediated by CD4+ and CD8+ T cells. A lower number of responders is found compared to homemade-IGRA-SPIKE test, likely due to the different peptide composition.

5.
Clinical Immunology ; : 109103, 2022.
Article in English | ScienceDirect | ID: covidwho-2003937

ABSTRACT

The severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) survivors are more likely to produce a potent immune response to SARS-CoV-2 after booster vaccination. We assessed humoral and T cell responses against SARS-CoV-2 in previously vaccinated SARS-CoV-1 survivors and naïve healthy individuals (NHIs) after a booster Ad5-nCoV dose. Boosted SARS-CoV-1 survivors had a high neutralization of SARS-CoV-2 Wuhan-Hu-1 (WA1), Beta, and Delta but is limited to Omicron subvariants (BA.1, BA.2, BA.2.12.1, and BA.4/5). Most boosted SARS-CoV-1 survivors had robust SARS-CoV-2-specific CD4+ and CD8+ T cell responses. While booster vaccination in NHIs elicited less or ineffective neutralization of WA1, Beta, and Delta, and none of them induced neutralizing antibodies against Omicron subvariants. However, they developed comparable SARS-CoV-2-specific T cell responses compared to boosted SARS-CoV-1 survivors. These findings suggest that boosted Ad5-nCoV would not elicit effective neutralizing antibodies against Omicron subvariants in SARS-CoV-1 survivors and NHIs but induced comparable robust T cell responses. Achieving a high antibody titer in SARS-CoV-1 survivors and NHIs is desirable to generate broad neutralization.

6.
Diagnostics (Basel) ; 12(6)2022 Jun 20.
Article in English | MEDLINE | ID: covidwho-1969126

ABSTRACT

Since the identification of the new severe acute respiratory syndrome virus 2 (SARS-CoV-2), a huge effort in terms of diagnostic strategies has been deployed. To date, serological assays represent a valuable tool for the identification of recovered COVID-19 patients and for the monitoring of immune response elicited by vaccination. However, the role of T-cell response should be better clarified and simple and easy to perform assays should be routinely introduced. The main aim of this study was to compare a home-made assay for whole blood stimulation with a standardized ELISpot assay design in our laboratory for the assessment of spike-specific T-cell response in vaccinated subjects. Even if a good correlation between the assays was reported, a higher percentage of responder subjects was reported for immunocompromised subjects with ELISpot assay (56%) than home-made whole blood stimulation assay (33%). Additionally, three commercial assays were compared with our home-made assay, reporting a good agreement in terms of both positive and negative results.

7.
Clin Chim Acta ; 532: 130-136, 2022 Jul 01.
Article in English | MEDLINE | ID: covidwho-1966414

ABSTRACT

Both infection with and vaccination against SARS-CoV-2 trigger a complex B-cell and T-cell response. Methods for the analysis of the B-cell response are now well established. However, reliable methods for measuring the T-cell response are less well established and their usefulness in clinical settings still needs to be proven. Here, we have developed and validated a T-cell proliferation assay based on 3H thymidine incorporation. The assay is using SARS-CoV-2 derived peptide pools that cover the spike (S), the nucleocapsid (N) and the membrane (M) protein for stimulation. We have compared this novel SARS-CoV-2 lymphocyte transformation test (SARS-CoV-2 LTT) to an established ELISA assay detecting Immunoglobulin G (IgG) antibodies to the S1 subunit of the SARS-CoV-2 spike protein. The study was carried out using blood samples from both vaccinated and infected health care workers as well as from a non-infected control group. Our novel SARS-CoV-2 LTT shows excellent discrimination of infected and/or vaccinated individuals versus unexposed controls, with the ROC analysis showing an area under the curve (AUC) of > 0.95. No false positives were recorded as all unexposed controls had a negative LTT result. When using peptide pools not only representing the S protein (found in all currently approved vaccines) but also the N and M proteins (not contained in the vast majority of vaccines), the novel SARS-CoV-2 LTT can also discriminate T-cell responses resulting from vaccination against those induced by infection.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , COVID-19/diagnosis , Cell Proliferation , Humans , Peptides , Spike Glycoprotein, Coronavirus , T-Lymphocytes , Vaccination
8.
Vaccines (Basel) ; 10(7)2022 Jul 15.
Article in English | MEDLINE | ID: covidwho-1939053

ABSTRACT

BACKGROUND AND OBJECTIVE: This prospective cohort study analyzed the immune response to COVID-19 mRNA vaccines in lung transplant recipients (LuTRs) compared to healthy controls (HCs) at a 6-month follow-up. METHODS: After the first two doses of either BNT162b2 or mRNA-1273, SARS-CoV-2 antibodies were measured in LuTRs (n = 57) and sex- and age-matched HCs (n = 57). Antibody kinetics during a 6-month follow-up and the effect of a third vaccine dose were evaluated. Humoral responses were assessed using the Elecsys® Anti-SARS-CoV-2 S immunoassay. In 16 LuTRs, SARS-CoV-2-specific T cell responses were quantified using IFN-γ ELISpot assays. RESULTS: Seroconversion rates were 94% and 100% after the first and second vaccine dose, respectively, in HCs, while only 19% and 56% of LuTRs developed antibodies. Furthermore, 22 of 24 LuTRs who received the third vaccine dose showed seroconversion (five of seven primary non-responders and 17 of 17 primary responders). A T cell response against SARS-CoV-2-spike S1 and/or S2 was detected in 100% (16/16) of HCs and 50% (8/16) of LuTRs. CONCLUSIONS: The data suggest that LuTRs have reduced humoral and cellular immune responses after two doses of COVID-19 mRNA vaccination when compared to HCs. A third dose may be of substantial benefit.

9.
Viruses ; 14(7)2022 07 19.
Article in English | MEDLINE | ID: covidwho-1939026

ABSTRACT

Omicron BA.1 variant can readily infect people with vaccine-induced or naturally acquired SARS-CoV-2 immunity facilitated by escape from neutralizing antibodies. In contrast, T-cell reactivity against the Omicron BA.1 variant seems relatively well preserved. Here, we studied the preexisting T cells elicited by either vaccination with the mRNA-based BNT162b2 vaccine or by natural infection with ancestral SARS-CoV-2 for their cross-reactive potential to 20 selected CD4+ T-cell epitopes of spike-protein-harboring Omicron BA.1 mutations. Although the overall memory CD4+ T-cell responses primed by the ancestral spike protein was still preserved generally, we show here that there is also a clear loss of memory CD4+ T-cell cross-reactivity to immunodominant epitopes across the spike protein due to Omicron BA.1 mutations. Complete or partial loss of preexisting T-cell responsiveness was observed against 60% of 20 nonconserved CD4+ T-cell epitopes predicted to be presented by a broad set of common HLA class II alleles. Monitoring such mutations in circulating strains helps predict which virus variants may escape previously induced cellular immunity and could be of concern.


Subject(s)
COVID-19 , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , T-Lymphocytes , Antibodies, Neutralizing , Antibodies, Viral , BNT162 Vaccine , COVID-19/immunology , COVID-19/prevention & control , Epitopes, T-Lymphocyte/genetics , Humans , Membrane Glycoproteins , Mutation , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , T-Lymphocytes/immunology , Viral Envelope Proteins/genetics
10.
Cell Rep Med ; 3(8): 100697, 2022 Aug 16.
Article in English | MEDLINE | ID: covidwho-1915084

ABSTRACT

The current strategy to detect immunodominant T cell responses focuses on the antigen, employing large peptide pools to screen for functional cell activation. However, these approaches are labor and sample intensive and scale poorly with increasing size of the pathogen peptidome. T cell receptors (TCRs) recognizing the same epitope frequently have highly similar sequences, and thus, the presence of large sequence similarity clusters in the TCR repertoire likely identify the most public and immunodominant responses. Here, we perform a meta-analysis of large, publicly available single-cell and bulk TCR datasets from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals to identify public CD4+ responses. We report more than 1,200 αßTCRs forming six prominent similarity clusters and validate histocompatibility leukocyte antigen (HLA) restriction and epitope specificity predictions for five clusters using transgenic T cell lines. Collectively, these data provide information on immunodominant CD4+ T cell responses to SARS-CoV-2 and demonstrate the utility of the reverse epitope discovery approach.

11.
Clin Microbiol Rev ; : e0001422, 2022 Jun 06.
Article in English | MEDLINE | ID: covidwho-1896040

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps evolving and mutating into newer variants over time, which gain higher transmissibility, disease severity, and spread in communities at a faster rate, resulting in multiple waves of surge in Coronavirus Disease 2019 (COVID-19) cases. A highly mutated and transmissible SARS-CoV-2 Omicron variant has recently emerged, driving the extremely high peak of infections in almost all continents at an unprecedented speed and scale. The Omicron variant evades the protection rendered by vaccine-induced antibodies and natural infection, as well as overpowers the antibody-based immunotherapies, raising the concerns of current effectiveness of available vaccines and monoclonal antibody-based therapies. This review outlines the most recent advancements in studying the virology and biology of the Omicron variant, highlighting its increased resistance to current antibody-based therapeutics and its immune escape against vaccines. However, the Omicron variant is highly sensitive to viral fusion inhibitors targeting the HR1 motif in the spike protein, enzyme inhibitors, involving the endosomal fusion pathway, and ACE2-based entry inhibitors. Omicron variant-associated infectivity and entry mechanisms of Omicron variant are essentially distinct from previous characterized variants. Innate sensing and immune evasion of SARS-CoV-2 and T cell immunity to the virus provide new perspectives of vaccine and drug development. These findings are important for understanding SARS-CoV-2 viral biology and advances in developing vaccines, antibody-based therapies, and more effective strategies to mitigate the transmission of the Omicron variant or the next SARS-CoV-2 variant of concern.

12.
Diagnostics (Basel) ; 12(6)2022 Jun 09.
Article in English | MEDLINE | ID: covidwho-1884057

ABSTRACT

OBJECTIVE: As we progress with mass vaccination against SARS-CoV-2, there are key questions about the immunogenicity of COVID-19 vaccines that still are not answered. Conventional methods to measure cellular immune responses are complex and expensive in a pandemic situation. PATIENTS AND METHODS: Forty healthy healthcare workers accepted to participate during the vaccination schedule with a mRNA vaccine against SARS-CoV-2. Measurement of Delayed-Type Hypersensitivity (DTH) cutaneous response after intradermal test of protein S of SARS-CoV-2 at day 35 and day 200 was performed. At the same time, a specific anti-RBD IgG using a classic ELISA before vaccination, and on days 0, 35, and 200 was performed. RESULTS: All 40 individuals had a positive DTH skin response at day 35, whereas 39 participants had a positive skin test at day 200. Moreover, although all 40 individuals showed a positive humoral response of specific IgG against spike protein at day 35, with most of them having significantly lower levels at day 200. CONCLUSION: DTH could be proposed as an ideal and easy method to predict cellular immunity response to mRNA vaccines 200 days after starting an immunization schedule with mRNA vaccine for COVID-19.

13.
Br J Haematol ; 198(4): 668-679, 2022 08.
Article in English | MEDLINE | ID: covidwho-1874397

ABSTRACT

Allogeneic haematopoietic stem cell transplant (HSCT) recipients remain at high risk of adverse outcomes from coronavirus disease 2019 (COVID-19) and emerging variants. The optimal prophylactic vaccine strategy for this cohort is not defined. T cell-mediated immunity is a critical component of graft-versus-tumour effect and in determining vaccine immunogenicity. Using validated anti-spike (S) immunoglobulin G (IgG) and S-specific interferon-gamma enzyme-linked immunospot (IFNγ-ELIspot) assays we analysed response to a two-dose vaccination schedule (either BNT162b2 or ChAdOx1) in 33 HSCT recipients at ≤2 years from transplant, alongside vaccine-matched healthy controls (HCs). After two vaccines, infection-naïve HSCT recipients had a significantly lower rate of seroconversion compared to infection-naïve HCs (25/32 HSCT vs. 39/39 HCs no responders) and had lower S-specific T-cell responses. The HSCT recipients who received BNT162b2 had a higher rate of seroconversion compared to ChAdOx1 (89% vs. 74%) and significantly higher anti-S IgG titres (p = 0.022). S-specific T-cell responses were seen after one vaccine in HCs and HSCT recipients. However, two vaccines enhanced S-specific T-cell responses in HCs but not in the majority of HSCT recipients. These data demonstrate limited immunogenicity of two-dose vaccination strategies in HSCT recipients, bolstering evidence of the need for additional boosters and/or alternative prophylactic measures in this group.


Subject(s)
COVID-19 Vaccines , COVID-19 , Hematopoietic Stem Cell Transplantation , Age Factors , Antibodies, Viral/immunology , BNT162 Vaccine/immunology , BNT162 Vaccine/therapeutic use , Bone Marrow Transplantation/adverse effects , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , COVID-19 Vaccines/pharmacology , COVID-19 Vaccines/therapeutic use , ChAdOx1 nCoV-19/immunology , ChAdOx1 nCoV-19/therapeutic use , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Immunity, Cellular/drug effects , Immunity, Cellular/immunology , Immunity, Humoral/drug effects , Immunity, Humoral/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Seroconversion , Transplantation, Homologous/adverse effects , Vaccination/adverse effects
14.
Biosaf Health ; 4(3): 179-185, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1872950

ABSTRACT

Like antibody evaluation, using an effective antigen-specific T-cell immunity assessment method in coronavirus disease 2019 (COVID-19) patients, survivors and vaccinees is crucial for understanding the immune persistence, prognosis assessment, and vaccine development for COVID-19. This study evaluated an empirically adjusted enzyme-linked immunospot assay for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T-cell immunity in 175 peripheral blood samples from COVID-19 convalescents and healthy individuals. Results of viral nucleic acid were used as the gold standard of infection confirmation. The SARS-CoV-2M peptide pool had higher sensitivity of 85% and specificity of 71% for the single peptide pool. For combined peptide pools, the parallel evaluation (at least one of the peptide pools is positive) of total peptide pools (S1&S2&M&N) had higher sensitivity (up to 93%), and the serial evaluation (all peptide pools are positive) of total peptide pools had higher specificity (up to 100%). The result of the serial evaluation was better than that of the parallel evaluation as a whole. The detection efficiency of M and N peptide pool serial evaluation appeared the highest, with a sensitivity of 80% and specificity of 93%. This T-cell immunity detection assay introduced in this report can achieve high operability and applicability. Therefore, it can be an effective SARS-CoV-2-specific cellular immune function evaluation method.

15.
Vaccines (Basel) ; 10(5)2022 May 09.
Article in English | MEDLINE | ID: covidwho-1862946

ABSTRACT

mRNA vaccines have been shown to be safe and effective in individuals with cancer. It is unclear, however, if systemic anti-cancer therapy impacts the coordinated cellular and humoral immune responses elicited by SARS-CoV-2 mRNA vaccines. To fill this knowledge gap, we assessed SARS-CoV-2 mRNA vaccine-elicited immunity in a cohort of patients with advanced solid tumors either under observation or receiving systemic anti-cancer therapy. This analysis revealed that SARS-CoV-2 mRNA vaccine-elicited cellular and humoral immunity was not significantly different in individuals with cancer receiving systemic anti-cancer therapy relative to individuals under observation. Furthermore, even though some patients exhibited suboptimal antibody titers after vaccination, SARS-CoV-2 specific cellular immune responses were still detected. These data suggest that antibody titers offer an incomplete picture of vaccine-elicited SARS-CoV-2 immunity in cancer patients undergoing active systemic anti-cancer therapy, and that vaccine-elicited cellular immunity exists even in the absence of significant quantities of SARS-CoV-2 specific antibodies.

16.
Int J Infect Dis ; 121: 24-30, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1859786

ABSTRACT

OBJECTIVES: We assessed vaccination-induced antibody and cellular responses against spike from the ancestral strain and from the delta (δ) SARS-CoV-2 variant in patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressive therapy in comparison with immunocompetent subjects. METHODS: We enrolled patients with IMID and immunocompetent subjects who completed the vaccination schedule within 4-6 months from the first dose. The interferon (IFN)-γ-response to spike peptides that were derived from the ancestral and the δ SARS-CoV-2 were measured by ELISA. Anti-Receptor Binding Domain IgG antibodies were also evaluated. RESULTS: We enrolled 43 patients with IMID and nine immunocompetent subjects. No significant differences were found after comparing the specific immune response (IFN-γ) between patients with IMID and immunocompetent subjects to the ancestral (p = 0.36) or δ peptide pool (p = 0.51). Nevertheless, IFN-γ-specific responses to the ancestral or to the δ pools were reduced in subjects taking CTLA4-IgG or TNF-α inhibitors compared with subjects treated with IL-6 inhibitors or Disease Modifying Anti-Rheumatic Drugs. Regarding the antibody response, no significant differences were observed between patients with IMID and immunocompetent individuals. CONCLUSIONS: Cellular responses to δ SARS-CoV-2 variant remain largely intact in patients with IMID. However, the magnitude of these responses is dependent on the specific IMID immunosuppressive regimen. Serological response was also similar between the IMID and control groups.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Antibody Formation , COVID-19/prevention & control , Humans , Immunity, Humoral , Immunoglobulin G
17.
Clinical and Experimental Vaccine Research ; 11(1):121-124, 2022.
Article in English | ProQuest Central | ID: covidwho-1857371

ABSTRACT

Knowledge about mRNA-1273 elicited T-cell response is limited. We investigated adverse reactions and interferon gamma release by specific T-cells among mRNA-1273 vaccinated health care workers. Seven to 13 weeks after complete vaccination low levels of specific T-cells were detected not correlating with antibody response. Severity of symptoms after first and number of symptoms after second immunization were associated with T-cell response. Assessment of T-cell response in addition to antibody response is crucial because even few specific T-cells could add to protection against infection. Investigation of mRNA-1273 induced inflammatory processes might help improve reactogenicity and immunogenicity.

18.
Vaccines (Basel) ; 10(5)2022 May 16.
Article in English | MEDLINE | ID: covidwho-1855859

ABSTRACT

Emerging numbers of SARS-CoV-2 infections are currently combated with a third vaccination. Considering the different vaccination regimens used for the first two vaccine doses, we addressed whether the previous vaccination influences the immune response to the booster. Participants for this prospective study were recruited from among healthcare workers. N = 20 participants were previously vaccinated with two doses of BNT162b2, and n = 53 received a priming dose of ChAdOx1-nCoV-19 followed by a BNT162b2 dose. Participants were vaccinated with a third dose of BNT162b2 in December 2021. Antibody concentrations were determined after vaccination, and in a subset of n = 19 participants, T cell responses were evaluated. Anti-S concentrations and IFNγ production increased during the first 21 days. The choice of the first and second vaccineshad no influence on the final outcome of the booster vaccination. Before booster vaccination, antibody concentrations were lower for older participants but increased more strongly over time.

19.
Allergol Immunopathol (Madr) ; 50(3): 101-105, 2022.
Article in English | MEDLINE | ID: covidwho-1836059

ABSTRACT

BACKGROUND: Patients with primary antibody deficiencies, such as Common Variable Immunodeficiency (CVID), have some problems to assess immune response after coronavirus disease (COVID) vaccination. Cutaneous delayed-type hypersensitivity (DTH) has the potential to be used as a useful, simple, and cheaper tool to assess T-cell (T lymphocyte) function. METHODS: Seventeen patients with CVID, a rare disease, received two doses of the mRNA-based Pfizer-BioNTech COVID-19 vaccine. Humoral Immune Response (HIR) was determined by measuring specific immunoglobulin G (IgG) antibodies, and Cellular Immune Response (CIR) was evaluated using an ex vivo interferon-gamma release assay (IGRA) and in vivo by DTH skin test. RESULTS: Two weeks after the second dose of the vaccine, 12 out of 17 CVID patients have high optical density (OD) ratios of specific anti-spike protein (S) IgG whereas five patients were negative or low. Ex vivo CIR was considered positive in 14 out of 17 S1-stimulated patients. Unspecific stimulation was positive in all 17 patients showing no T-cell defect. A positive DTH skin test was observed in 16 CVID patients. The only patient with negative DTH also had negative ex vivo CIR. CONCLUSIONS: The use of DTH to evaluate CIR was validated with an optimal correlation with the ex vivo CIR. The CIR after vaccination in patients with antibody deficiencies seems to have high precision and more sensitivity to antibodies-based methods in CVID. CLINICAL IMPLICATIONS: There is a remarkable correlation between cutaneous DTH and ex vivo IGRA after COVID vaccination. A COVID-specific skin DTH test could be implemented in large populations. CAPSULE SUMMARY: Cutaneous delayed-type hypersensitivity has the potential to be used as a useful, simple, and cheaper tool to assess T-cell functioning.


Subject(s)
COVID-19 , Common Variable Immunodeficiency , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunity, Cellular , Immunity, Humoral , Immunoglobulin G , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccination
20.
Front Immunol ; 13: 875236, 2022.
Article in English | MEDLINE | ID: covidwho-1834410

ABSTRACT

A variety of methods have been explored to increase delivery efficiencies for DNA vaccine. However, the immunogenicity of DNA vaccines has not been satisfactorily improved. Unlike most of the previous attempts, we provided evidence suggesting that changing the injection site successively (successively site-translocated inoculation, SSTI) could significantly enhance the immunogenicity of DNA vaccines in a previous study. To simplify the strategy and to evaluate its impact on candidate SARS-CoV-2 vaccines, we immunized mice with either a SARS-CoV-2 spike-based DNA vaccine or a spike protein subunit vaccine via three different inoculation strategies. Our data demonstrated that S protein specific antibody responses elicited by the DNA vaccine or the protein subunit vaccine showed no significant difference among different inoculation strategies. Of interest, compared with the conventional site fixed inoculation (SFI), both successive site-translocating inoculation (SSTI) and the simplified translocating inoculation (STI) strategy improved specific T cell responses elicited by the DNA vaccine. More specifically, the SSTI strategy significantly improved both the monofunctional (IFN-γ+IL-2-TNF-α-CD8+) and the multifunctional (IFN-γ+IL-2-TNF-α+CD8+, IFN-γ+IL-2-TNF-α+CD4+, IFN-γ+IL-2+TNF-α+CD4+) T cell responses, while the simplified translocating inoculation (STI) strategy significantly improved the multifunctional CD8+ (IFN-γ+IL-2-TNF-α+CD8+, IFN-γ+IL-2+TNF-α+CD8+) and CD4+ (IFN-γ+IL-2-TNF-α+CD4+, IFN-γ+IL-2+TNF-α+CD4+) T cell responses. The current study confirmed that changing the site of intra muscular injection can significantly improve the immunogenicity of DNA vaccines.


Subject(s)
COVID-19 , Sexually Transmitted Diseases , Vaccines, DNA , Animals , CD4-Positive T-Lymphocytes , CD8-Positive T-Lymphocytes , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Interleukin-2 , Mice , Protein Subunits , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Tumor Necrosis Factor-alpha
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