Persistent T-Cell Reactivity in a Seronegative Patient after SARS-CoV-2 Infection and One Vaccination

We present here a 64-year-old male participant of the CoNAN study who experienced a PCR-confirmed mild SARS-CoV-2 infection but did not develop any measurable antibody response. Additionally, after vaccination with ChAdOx1 (AstraZeneca, Cambridge, UK) 11 months later, no antibodies were detected in six serological tests three weeks after the vaccination. When we assessed T-helper (Th) cell immunity, SARS-CoV-2-specific Th cells produced detectable amounts of IFNγ and TNF six weeks after the infection. A robust T-cell immunity remained detectable at least until six months after the infection and was boosted by the vaccination thereafter. This case report points out that an assessment of a prior infection or a vaccine response based solely on antibody detection might have limitations in individual patients.

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Evaluation of T Cell Immunity against Human Cytomegalovirus: Impact on Patient Management and Risk Assessment of Vertical Transmission

Journal of Immunology Research ◽

10.1155/2016/9384813 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 5

Author(s):

Giulia Freer ◽

Paola Quaranta ◽

Mauro Pistello

Keyword(s):

T Cell ◽

Solid Organ Transplantation ◽

Solid Organ ◽

Infectious Agents ◽

Cmv Infection ◽

Active Infection ◽

Cell Reactivity ◽

Cell Immunity ◽

Pros And Cons ◽

T Cell Reactivity

Cytomegalovirus (CMV) is one of the most common infectious agents, infecting the general population at an early age without causing morbidity most of the time. However, on particular occasions, it may represent a serious risk, as active infection is associated with rejection and disease after solid organ transplantation or fetal transmission during pregnancy. Several methods for CMV diagnosis are available on the market, but because infection is so common, careful selection is needed to discriminate primary infection from reactivation. This review focuses on methods based on CMV-specific T cell reactivity to help monitor the consequences of CMV infection/reactivation in specific categories of patients. This review makes an attempt at discussing the pros and cons of the methods available.

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Impact of pre-existing T cell immunity to SARS-CoV-2 in uninfected individuals with COVID-19 mortality in different countries

10.1101/2020.10.03.20206151 ◽

2020 ◽

Author(s):

Gennadi V. Glinsky

Keyword(s):

T Cells ◽

T Cell ◽

Herd Immunity ◽

Inverse Correlation ◽

Mortality Rates ◽

Virus Spread ◽

Cell Reactivity ◽

Cell Immunity ◽

Potential Impact ◽

T Cell Reactivity

AbstractSeveral recent studies identified SARS-CoV-2 reactive T cells in people without exposure to the virus. However, pathophysiological implications of these findings remain unknown. Here, the potential impact of pre-existing T cell reactivity against SARS-CoV-2 in uninfected individuals on markedly different COVID-19 mortality levels in different countries has been investigated. The inverse correlation is documented between the prevalence of pre-existing SARS-CoV-2 reactive T cells in people without exposure to the virus and COVID-19 mortality rates in different countries. In countries with similar levels of pre-existing SARS-CoV-2 cross-reactive T cells in uninfected individuals, differences in COVID-19 mortality appear linked with the extend and consistency of implementations of social measures designed to limit the transmission of SARS-CoV-2 (lockdown; physical distancing; mask wearing). Collectively, these observations support the model that the level of pre-existing SARS-CoV-2 reactive T cells is one of the important determinants of the innate herd immunity against COVID-19. Together with the consistent social measures directed to limit the virus spread, high levels of pre-existing SARS-CoV-2 reactive T cells appear significant determinants diminishing the COVID-19 mortality. Observations reported in this contribution should have significant impact on definitions of the herd immunity threshold required to effectively stop the pandemic in different countries across the globe.

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Preserved T cell reactivity to the SARS-CoV-2 Omicron variant indicates continued protection in vaccinated individuals.

10.1101/2021.12.30.474453 ◽

2021 ◽

Author(s):

Lorenzo De Marco ◽

Silvia D'Orso ◽

Marta Pirronello ◽

Alice Verdiani ◽

Andrea Termine ◽

...

Keyword(s):

T Cell ◽

Severe Disease ◽

Spike Protein ◽

Immune Recognition ◽

Immune Protection ◽

Cell Reactivity ◽

Cell Responses ◽

Cell Immunity ◽

T Cell Reactivity ◽

Study Setting

Importance: The emergence of the highly contagious Omicron variant of SARS-CoV-2 and the findings of a significantly reduced neutralizing potency of sera from convalescent or vaccinated individuals imposes the study of cellular immunity to predict the degree of immune protection to the yet again new coronavirus. Design: Prospective monocentric observational study. Setting: Conducted between December 20-21 at the Santa Lucia Foundation IRCCS. Participants: 61 volunteers (Mean age 41.62, range 21-62; 38F/23M) with different vaccination and SARS-CoV-2 infection backgrounds donated 15 ml of blood. Of these donors, one had recently completed chemotherapy, and one was undergoing treatment with monoclonal antibodies; the others reported no known health issue. Main Outcome(s) and Measure(s): The outcomes were the measurement of T cell reactivity to the mutated regions of the Spike protein of the Omicron SARS-CoV-2 variant and the assessment of remaining T cell immunity to the spike protein by stimulation with peptide libraries. Results: Lymphocytes from freshly drawn blood samples were isolated and immediately tested for reactivity to the Spike protein of SARS-CoV-2. T cell responses to peptides covering the mutated regions in the Omicron variant were decreased by over 47% compared to the same regions of the ancestral vaccine strain. However, overall reactivity to the peptide library of the full-length protein was largely maintained (estimated 83%). No significant differences in loss of immune recognition were identified between groups of donors with different vaccination and/or infection histories. Conclusions and Relevance: We conclude that despite the mutations in the Spike protein, the SARS-CoV-2 Omicron variant is nonetheless recognized by the cellular component of the immune system. It is reasonable to assume that protection from hospitalization and severe disease is maintained.

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Immunodominant T-cell epitopes from the SARS-CoV-2 spike antigen reveal robust pre-existing T-cell immunity in unexposed individuals

Scientific Reports ◽

10.1038/s41598-021-92521-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Swapnil Mahajan ◽

Vasumathi Kode ◽

Keshav Bhojak ◽

Coral Karunakaran ◽

Kayla Lee ◽

...

Keyword(s):

T Cell ◽

T Cell Activation ◽

Cell Activation ◽

Cd8 T Cell ◽

T Cell Immunity ◽

T Cell Epitopes ◽

Cell Reactivity ◽

Cell Immunity ◽

T Cell Reactivity ◽

Shared Epitopes

AbstractThe COVID-19 pandemic has revealed a range of disease phenotypes in infected patients with asymptomatic, mild, or severe clinical outcomes, but the mechanisms that determine such variable outcomes remain unresolved. In this study, we identified immunodominant CD8 T-cell epitopes in the spike antigen using a novel TCR-binding algorithm. The predicted epitopes induced robust T-cell activation in unexposed donors demonstrating pre-existing CD4 and CD8 T-cell immunity to SARS-CoV-2 antigen. The T-cell reactivity to the predicted epitopes was higher than the Spike-S1 and S2 peptide pools in the unexposed donors. A key finding of our study is that pre-existing T-cell immunity to SARS-CoV-2 is contributed by TCRs that recognize common viral antigens such as Influenza and CMV, even though the viral epitopes lack sequence identity to the SARS-CoV-2 epitopes. This finding is in contrast to multiple published studies in which pre-existing T-cell immunity is suggested to arise from shared epitopes between SARS-CoV-2 and other common cold-causing coronaviruses. However, our findings suggest that SARS-CoV-2 reactive T-cells are likely to be present in many individuals because of prior exposure to flu and CMV viruses.

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The landscape of T cell epitope immunogenicity in sequence space

10.1101/155317 ◽

2017 ◽

Cited By ~ 1

Author(s):

Masato Ogishi ◽

Hiroshi Yotsuyanagi

Keyword(s):

T Cell ◽

Cell Epitope ◽

Cell Receptor ◽

Single Amino Acid ◽

Cell Reactivity ◽

Human T Cell ◽

Cell Immunity ◽

Tcr Repertoire ◽

Individualized Approach ◽

T Cell Reactivity

SummaryThe existence of population-wide T cell immunity is widely recognized for multiple pathogen-derived immunodominant epitopes, despite the vast diversity and individualized nature of T cell receptor (TCR) repertoire. We thus hypothesized that population-wide epitope immunogenicity could be probabilistically defined by exploiting public TCR features. To gain a proof-of-concept, here we describe a machine learning framework yielding probabilistic estimates of immunogenicity, termed “immunogenicity scores”, by utilizing features designed to mimic thermodynamic interactions between peptides bound to major histocompatibility complex (MHC) and TCR repertoire. Immunogenicity score dynamics among observed and computationally simulated single amino acid mutants delineated the landscape of position- and residue-specific mutational impacts, and even quantitatively estimated escaping potentials of known epitopes with remarkable positional specificity. This study illustrates that the population-wide aspect of adaptive immunity is predictable via non-individualized approach, possibly indicating antigen-guided convergence of human T cell reactivity.

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T-CELL REACTIVITY TO ANTIGENS OF STREPTOCOCCUS IN ERYZIPELAS PATIENTS ON LASER THERAPY

Epidemiology and Infectious Diseases (Russian Journal) ◽

10.18821/1560-9529-2019-24-2-69-76 ◽

2019 ◽

Vol 24 (2) ◽

pp. 69-76

Author(s):

Olga F. Belaia ◽

S. A. Potekaeva ◽

E. V. Volchkova ◽

O. A. Payevskaya ◽

S. N. Zuevskaya ◽

...

Keyword(s):

T Cell ◽

Laser Therapy ◽

Screening Method ◽

Surface Proteins ◽

Leukocyte Migration ◽

Cell Reactivity ◽

Cell Immunity ◽

Specific Antigens ◽

T Cell Reactivity

Erysipelas is a widespread infectious disease, with severe hemorrhagic forms, frequent recurrence and complications. Activation of T-cell immunity by individual streptococcus antigens determines the nature of the course and outcomes of erysipelas. Laser therapy is widely used in the treatment of erysipelas, however, indications for its purpose are often empirical, laboratory criteria for indications for purpose are absent. The goal is to study the effectiveness of infrared laser therapy in terms of the dynamics of leukocyte migration in vitro in response to S. pyogenes antigens. Materials and methods. 95 patients with erysipelas (55 women and 40 men) aged 20-65 years were examined, of which 34 were with primary erysipelas of extremity, 23 were with face erysipelas, 39 were with relapsed l erysipelas of extremity. All patients received basic antibiotic therapy. Laser therapy of the local focus area was performed in 30 of them. The leukocyte migration is determined in vitro by screening test of cell migration (STCM) during stimulation with polysaccharide, surface proteins, and the antigen of L-forms of S. pyogenes in various concentrations. Results. Laser therapy of patients with erysipelas had a noticeable immunomodulatory effect in the reaction of blood cells to the polysaccharide and surface proteins. At the same time, in patients with erythematous-hemorrhagic form of erysipelas, the clinical effect was manifested in a shorter duration of erythema, edema, hemorrhages, and regional lymphadenitis. Conclusion. The STCM method, which makes it possible to evaluate the migration of leukocytes to the surface specific antigens of streptococcus, can be used as a screening method for patients with erysipelas, in whom laser therapy may have a more pronounced effect.

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