Defending against SARS-CoV-2: The T cell perspective

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Jan. 27, 2023

SARS-CoV-2-specific T cell response has been proven essential for viral clearance, COVID-19 outcome and long-term memory. Impaired early cell-driven immunity leads to a severe form of the disease associated with lymphopenia, hyperinflammation imbalanced humoral response. Analyses acute SARS-CoV-2 infection have revealed that mild course is characterized by an induction specific cells within first 7 days symptoms, coordinately followed antibody production effective control infection. In contrast, patients who do not develop cellular initiate immune subsequent high levels antibodies, symptoms. Yet, delayed persistent bystander CD8+ activation also reported in hospitalized could be driver lung pathology. Literature supports maintenance appears more stable than titters. Up date, virus-specific memory detected 22 months post-symptom onset, predominant IL-2 compared IFN-γ. Furthermore, responses are conserved against emerging variants concern (VoCs) while these mostly able evade responses. This partly explained HLA polymorphism whereby epitope repertoire recognized differ among individuals, greatly decreasing likelihood escape. Current COVID-19-vaccination shown elicit Th1-driven spike-specific response, as does natural infection, which provides substantial protection death. addition, mucosal vaccination induce strong adaptive both locally systemically protect VoCs animal models. The optimization vaccine formulations including variety regions, innovative adjuvants or diverse administration routes result desirable enhanced memory, help prevent breakthrough infections. summary, increasing evidence highlights relevance monitoring only levels, correlate after and/or vaccination. Moreover, it may better identify target populations benefit most from booster doses personalize strategies.

Language: Английский

---

T cell immune memory after covid-19 and vaccination

BMJ Medicine, Journal Year: 2023, Volume and Issue: 2(1), P. e000468 - e000468

Published: Nov. 1, 2023

The T cell memory response is a crucial component of adaptive immunity responsible for limiting or preventing viral reinfection. after infection with the SARS-CoV-2 virus vaccination broad, and spans multiple proteins epitopes, about 20 in each individual. So far long lasting provides high level cross reactivity hence resistance to escape by variants virus, such as omicron variant. All current vaccine regimens tested produce robust responses, heterologous will probably enhance protective responses through increased breadth. could have major role protecting against severe covid-19 disease rapid clearance early presentation presence reactive cells might this protection. likely provide ongoing protection admission hospital death, development pan-coronovirus future proof new pandemic strains.

Language: Английский

---

The Importance of Measuring SARS-CoV-2-Specific T-Cell Responses in an Ongoing Pandemic

Pathogens, Journal Year: 2023, Volume and Issue: 12(7), P. 862 - 862

Published: June 22, 2023

Neutralizing antibodies are considered a correlate of protection against SARS-CoV-2 infection and severe COVID-19, although they not the only contributing factor to immunity: T-cell responses important in protecting COVID-19 success vaccination effort. after largely mirror those natural magnitude functional capacity, but breadth, as T-cells induced by exclusively target surface spike glycoprotein. offer long-lived line defense and, unlike humoral responses, retain reactivity variants. Given increasingly recognized role circulation variants, potential implementation novel vaccines, it becomes imperative continuously monitor responses. In addition “classical” assays requiring isolation peripheral blood mononuclear cells, simple whole-blood-based interferon-γ release have routine response monitoring. These could be particularly useful for immunocompromised people other clinically vulnerable populations, where interactions between cellular immunity complex. As we continue live alongside importance considering whole, incorporating both is crucial.

Language: Английский

---

Importance, Applications and Features of Assays Measuring SARS-CoV-2 Neutralizing Antibodies

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5352 - 5352

Published: March 10, 2023

More than three years ago, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) caused unforeseen COVID-19 pandemic with millions of deaths. In meantime, SARS-CoV-2 has become endemic and is now part repertoire viruses causing seasonal severe respiratory infections. Due to several factors, among them development immunity through natural infection, vaccination current dominance seemingly less pathogenic strains belonging omicron lineage, situation stabilized. However, challenges remain possible new occurrence highly variants remains a threat. Here we review development, features importance assays measuring neutralizing antibodies (NAbs). particular focus on in vitro infection molecular interaction studying binding receptor domain (RBD) its cognate cellular ACE2. These assays, but not measurement SARS-CoV-2-specific per se, can inform us whether produced by convalescent or vaccinated subjects may protect against thus have potential predict risk becoming newly infected. This information extremely important given fact that considerable number subjects, vulnerable persons, respond poorly production antibodies. Furthermore, these allow determine evaluate virus-neutralizing capacity induced vaccines administration plasma-, immunoglobulin preparations, monoclonal antibodies, ACE2 synthetic compounds be used for therapy assist preclinical evaluation vaccines. Both types relatively quickly adapted emerging virus about magnitude cross-neutralization, which even estimate infected appearing variants. Given paramount discuss their specific features, advantages disadvantages, technical aspects yet fully resolved issues, such as cut-off levels predicting degree vivo protection.

Language: Английский

---

A quest for universal anti-SARS-CoV-2 T cell assay: systematic review, meta-analysis, and experimental validation

npj Vaccines, Journal Year: 2024, Volume and Issue: 9(1)

Published: Jan. 2, 2024

Abstract Measuring SARS-CoV-2-specific T cell responses is crucial to understanding an individual’s immunity COVID-19. However, high inter- and intra-assay variability make it difficult define cells as a correlate of protection against To address this, we performed systematic review meta-analysis 495 datasets from 94 original articles evaluating using three assays – Activation Induced Marker (AIM), Intracellular Cytokine Staining (ICS), Enzyme-Linked Immunospot (ELISPOT), defined each assay’s quantitative range. We validated these ranges samples 193 SARS-CoV-2-exposed individuals. Although IFNγ ELISPOT was the preferred assay, our experimental validation suggested that under-represented repertoire. Our data indicate combination AIM ICS or FluoroSpot assay would better represent frequency, polyfunctionality, compartmentalization antigen-specific responses. Taken together, results contribute defining propose choice can be employed understand cellular immune response viral diseases.

Language: Английский

---

Robust humoral and cellular recall responses to AZD1222 attenuate breakthrough SARS-CoV-2 infection compared to unvaccinated

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 13, 2023

Background Breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in disease 2019 (COVID-19) vaccinees typically produces milder than unvaccinated individuals. Methods To explore attenuation, we examined COVID-19 symptom burden and immuno-virologic responses to symptomatic SARS-CoV-2 participants (AZD1222: n=177/17,617; placebo: n=203/8,528) from a 2:1 randomized, placebo-controlled, phase 3 study of two-dose primary series AZD1222 (ChAdOx1 nCoV-19) vaccination (NCT04516746). Results We observed that had an overall lower incidence shorter duration symptoms compared with placebo recipients, as well viral loads median shedding saliva. Vaccinees demonstrated robust antibody recall response versus recipients low-to-moderate inverse correlations virologic endpoints. also enriched polyfunctional spike-specific Th-1-biased CD4+ CD8+ T-cell was associated strong Conclusion Robust immune following attenuate severity restrict transmission potential by reducing the Collectively, these analyses underscore essential role mitigating pandemic.

Language: Английский

---

Interim safety and immunogenicity analysis of the EuCorVac‐19 COVID‐19 vaccine in a Phase 3 randomized, observer‐blind, immunobridging trial in the Philippines

Journal of Medical Virology, Journal Year: 2024, Volume and Issue: 96(9)

Published: Sept. 1, 2024

Abstract EuCorVac‐19 (ECV‐19) is a recombinant receptor binding domain (RBD) COVID‐19 vaccine that displays the RBD (derived from SARS‐CoV‐2 Wuhan strain) on immunogenic liposomes. This study compares safety and immunogenicity of ECV‐19 to COVISHIELD TM (CS) adenoviral‐vectored vaccine. Interim analysis presented randomized, observer‐blind, immunobridging Phase 3 trial in Philippines 2600 subjects, with treatment biospecimen collection between October 2022 January 2023. Healthy male female adults who received investigational vaccines were 18 years older, randomly assigned ( n = 2004) or CS 596) groups. Immunization followed two‐injection, intramuscular regimen 4 weeks prime boost vaccination. Safety endpoints assessed all participants was carried out subset 585 290 groups). The primary immunological superiority neutralizing antibody response, as well noninferiority seroresponse rate (defined 4‐fold increase titers baseline). After vaccination, had lower incidence local solicited adverse events (AEs) (12.0% vs. 15.8%, p < 0.01), systemic AEs (13.1 17.4%, 0.01) relative CS. second injection, both overall (7.8% 7.6%). For assessment, 98% prior exposure (based presence anti‐nucleocapsid antibodies) at time initial immunization, without differing baseline levels microneutralization (MN) against strain two induced higher anti‐RBD IgG (1,464 355 BAU/mL, 0.001) response (1,303 494 MN titer, 0.001). maintained those (1367 344 antibodies (1128 469 also elicited better neutralized Omicron variant, compared (763 373 Women displayed responses than men. group greater (83% 30%, In summary, favorable profiles, showing diminished AE after immunization. significantly terms IgG, antibodies, rate. These data establish relatively profile for ECV‐19. registered ClinicalTrials.gov (NCT05572879).

Language: Английский

---

Evaluation of T cell responses with the QuantiFERON SARS-CoV-2 assay in individuals with 3 doses of BNT162b2 vaccine, SARS-CoV-2 infection, or hybrid immunity

Diagnostic Microbiology and Infectious Disease, Journal Year: 2023, Volume and Issue: 106(3), P. 115948 - 115948

Published: March 30, 2023

Language: Английский

---

Predictors of reinfection with pre-Omicron and Omicron variants of concern among individuals who recovered from COVID-19 in the first year of the pandemic

International Journal of Infectious Diseases, Journal Year: 2023, Volume and Issue: 132, P. 72 - 79

Published: April 16, 2023

The predictors of SARS-CoV-2 reinfection are unclear. We examined with pre-Omicron and Omicron variants among COVID-19-recovered individuals.Randomly selected patients (N = 1004) who donated convalescent plasma during 2020 were interviewed between August 2021 March 2022 regarding COVID-19 vaccination laboratory-proven reinfection. sera from 224 (22.3%) participants tested for antispike (anti-S) immunoglobulin G neutralizing antibodies.The participants' median age was 31.1 years (78.6% males). overall incidence rate 12.8%; 2.7% versus 21.6% the (mostly Delta) variants. Negative associations found fever first illness reinfection: relative risk 0.29 (95% confidence interval 0.09-0.94), high anti-N level at 0.53 (0.33-0.85), 0.56 (0.37-0.84), as well subsequent BNT162b2 vaccine 0.15 (0.07-0.32), 0.48 (0.25-0.45), reinfections 0.38 (0.25-0.58). These variables significantly correlated anti-S follow-up levels. High pre-existing binding antibody levels against Wuhan Alpha strains predicted protection reinfections.Strong immune responses after infection provided cross-protection Delta

Language: Английский

---

Humoral and cell-mediated immune responses in HIV-vertically infected young patients after three doses of the BNT162b2 mRNA SARS-CoV-2 vaccine

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 4, 2024

Background Data on the efficacy of three SARS-CoV-2 mRNA BNT162b2 vaccine doses and role previous SARS-CoV-2-infection in enhancing immunogenicity HIV-vertically-infected people living with HIV (PLWH) are limited, as is duration vaccine-induced responses. Methods plasma neutralizing activity (NA) against European (B.1), Delta (B.1.617.2) Omicron (B.1.1.529) variants cell-mediated immunity (CMI) were analyzed 29 ART-treated young PLWH (mean age 27.9 years) 30 healthy controls (HC) who received doses. Individuals stratified based presence/absence infection (infected vaccinated -SIV-; uninfected -SV-). Analyses performed before vaccination (T0), 25 days from second dose (T1), day third was administered (T2), 3 months after (T3). Results In PLWH: i) NA all higher SIV compared to SV at T2 increased T3; ii) switched-memory plasmablasts augmented alone iii) a specific T cell memory generated; iv) IFN-γ-secreting CD4+ CD8+ lymphocytes boosted T3 mainly SV. CMI magnitude reduced HC. Notably, viremia unmodified, but CD4 counts reduced&gt;20% 3/29 PHLW. Conclusion A induces strong humoral responses independently natural infection. The lower should be considered when planning booster PLWH.

Language: Английский

---