Effective countermeasures against the recent emergence and rapid expansion of the 2019 novel coronavirus (SARS-CoV-2) require the development of data and tools to understand and monitor its spread ...and immune responses to it. However, little information is available about the targets of immune responses to SARS-CoV-2. We used the Immune Epitope Database and Analysis Resource (IEDB) to catalog available data related to other coronaviruses. This includes SARS-CoV, which has high sequence similarity to SARS-CoV-2 and is the best-characterized coronavirus in terms of epitope responses. We identified multiple specific regions in SARS-CoV-2 that have high homology to the SARS-CoV virus. Parallel bioinformatic predictions identified a priori potential B and T cell epitopes for SARS-CoV-2. The independent identification of the same regions using two approaches reflects the high probability that these regions are promising targets for immune recognition of SARS-CoV-2. These predictions can facilitate effective vaccine design against this virus of high priority.
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•Ten experimentally defined regions within SARS-CoV have high homology with SARS-CoV-2•Parallel bioinformatics predicted potential B and T cell epitopes for SARS-CoV-2•Independent approaches identified the same immunodominant regions•The conserved immune regions have implications for vaccine design against multiple CoVs
Grifoni et al. identify potential targets for immune responses to the 2019 novel coronavirus (SARS-CoV-2) by sequence homology with closely related SARS-CoV and by a priori epitope prediction using bioinformatics approaches. This analysis provides essential information for understanding human immune responses to this virus and for evaluating diagnostic and vaccine candidates.
DENV is a major public health problem worldwide, thus underlining the overall significance of the proposed Program. The four dengue virus (DENV) serotypes (1-4) cause the most common mosquito-borne ...viral disease of humans, with 3 billion people at risk for infection and up to 100 million cases each year, most often affecting children. The protective role of T cells during viral infection is well-established. Generally, CD8 T cells can control viral infection through several mechanisms, including direct cytotoxicity, and production of pro-inflammatory cytokines such as IFN-γ and TNF-α. Similarly, CD4 T cells are thought to control viral infection through multiple mechanisms, including enhancement of B and CD8 T cell responses, production of inflammatory and anti-viral cytokines, cytotoxicity, and promotion of memory responses. To probe the phenotype of virus-specific T cells, epitopes derived from viral sequences need to be known. Here we discuss the identification of CD4 and CD8 T cell epitopes derived from DENV and how these epitopes have been used by researchers to interrogate the phenotype and function of DENV-specific T cell populations.
The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron (B.1.1.529) variant of concern (VOC) has destabilized global efforts to control the impact of coronavirus ...disease 2019 (COVID-19). Recent data have suggested that B.1.1.529 can readily infect people with naturally acquired or vaccine-induced immunity, facilitated in some cases by viral escape from antibodies that neutralize ancestral SARS-CoV-2. However, severe disease appears to be relatively uncommon in such individuals, highlighting a potential role for other components of the adaptive immune system. We report here that SARS-CoV-2 spike-specific CD4
and CD8
T cells induced by prior infection or BNT162b2 vaccination provide extensive immune coverage against B.1.1.529. The median relative frequencies of SARS-CoV-2 spike-specific CD4
T cells that cross-recognized B.1.1.529 in previously infected or BNT162b2-vaccinated individuals were 84% and 91%, respectively, and the corresponding median relative frequencies for SARS-CoV-2 spike-specific CD8
T cells were 70% and 92%, respectively. Pairwise comparisons across groups further revealed that SARS-CoV-2 spike-reactive CD4
and CD8
T cells were functionally and phenotypically similar in response to the ancestral strain or B.1.1.529. Collectively, our data indicate that established SARS-CoV-2 spike-specific CD4
and CD8
T cell responses, especially after BNT162b2 vaccination, remain largely intact against B.1.1.529.
Understanding immune memory to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for improving diagnostics and vaccines and for assessing the likely future course of the ...COVID-19 pandemic. We analyzed multiple compartments of circulating immune memory to SARS-CoV-2 in 254 samples from 188 COVID-19 cases, including 43 samples at ≥6 months after infection. Immunoglobulin G (IgG) to the spike protein was relatively stable over 6+ months. Spike-specific memory B cells were more abundant at 6 months than at 1 month after symptom onset. SARS-CoV-2-specific CD4
T cells and CD8
T cells declined with a half-life of 3 to 5 months. By studying antibody, memory B cell, CD4
T cell, and CD8
T cell memory to SARS-CoV-2 in an integrated manner, we observed that each component of SARS-CoV-2 immune memory exhibited distinct kinetics.
SARS-CoV-2 messenger RNA vaccination in healthy individuals generates immune protection against COVID-19. However, little is known about SARS-CoV-2 mRNA vaccine-induced responses in immunosuppressed ...patients. We investigated induction of antigen-specific antibody, B cell and T cell responses longitudinally in patients with multiple sclerosis (MS) on anti-CD20 antibody monotherapy (n = 20) compared with healthy controls (n = 10) after BNT162b2 or mRNA-1273 mRNA vaccination. Treatment with anti-CD20 monoclonal antibody (aCD20) significantly reduced spike-specific and receptor-binding domain (RBD)-specific antibody and memory B cell responses in most patients, an effect ameliorated with longer duration from last aCD20 treatment and extent of B cell reconstitution. By contrast, all patients with MS treated with aCD20 generated antigen-specific CD4 and CD8 T cell responses after vaccination. Treatment with aCD20 skewed responses, compromising circulating follicular helper T (T
) cell responses and augmenting CD8 T cell induction, while preserving type 1 helper T (T
1) cell priming. Patients with MS treated with aCD20 lacking anti-RBD IgG had the most severe defect in circulating T
responses and more robust CD8 T cell responses. These data define the nature of the SARS-CoV-2 vaccine-induced immune landscape in aCD20-treated patients and provide insights into coordinated mRNA vaccine-induced immune responses in humans. Our findings have implications for clinical decision-making and public health policy for immunosuppressed patients including those treated with aCD20.
It is critically important to understand how the adaptive immune response, elicited by vaccination or infection, recognizes SARS-CoV-2. This is especially true when considering the challenges to the ...immune response posed by variant evolution. Herein, we summarize our work aimed at characterizing the magnitude of the CD4+ and CD8+ T cell responses to SARS-CoV-2, the proteins most frequently recognized, and the associated T cell epitope repertoire. This work formed the foundation for our most recent studies aimed at understanding and predicting the ability of T cell responses induced by SARS-CoV-2 infection or vaccination to subsequently cross-recognize novel SARS-CoV-2 variants. We found that T cell responses are remarkably preserved and able to cross-recognize SARS-CoV-2 variants, from Alpha to Omicron. This is distinct from what has been observed for the SARS-CoV-2- specific antibody and B cell responses. This body of work, supported by independent studies carried out by other groups, suggests that T cells may contribute to a second line of defense against infection while also limiting viral spread and, thus, disease severity.
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•TB and COVID-19 coinfection does not affect M. tuberculosis-specific response.•TB and COVID-19 coinfection limits the ability to in vitro respond to SARS-CoV-2.•Latent TB infection does not affect ...the ability to in vitro respond to SARS-CoV-2.
The interaction of COVID-19 and tuberculosis (TB) are still poor characterized. Here we evaluated the immune response specific for Micobacterium tuberculosis (Mtb) and SARS-CoV-2 using a whole-blood-based assay-platform in COVID-19 patients either with TB or latent TB infection (LTBI).
We evaluated IFN-γ level in plasma from whole-blood stimulated with Mtb antigens in the Quantiferon-Plus format or with peptides derived from SARS-CoV-2 spike protein, Wuhan-Hu-1 isolate (CD4-S).
We consecutively enrolled 63 COVID-19, 10 TB-COVID-19 and 11 LTBI-COVID-19 patients.
IFN-γ response to Mtb-antigens was significantly associated to TB status and therefore it was higher in TB-COVID-19 and LTBI-COVID-19 patients compared to COVID-19 patients (p ≤ 0.0007).
Positive responses against CD4-S were found in 35/63 COVID-19 patients, 7/11 LTBI-COVID-19 and only 2/10 TB-COVID-19 patients. Interestingly, the responders in the TB-COVID-19 group were less compared to COVID-19 and LTBI-COVID-19 groups (p = 0.037 and 0.044, respectively). Moreover, TB-COVID-19 patients showed the lowest quantitative IFN-γ response to CD4-S compared to COVID-19-patients (p = 0.0336) and LTBI-COVID-19 patients (p = 0.0178).
Our data demonstrate that COVID-19 patients either TB or LTBI have a low ability to build an immune response to SARS-CoV-2 while retaining the ability to respond to Mtb-specific antigens.
We enrolled healthy subjects that received 2 to 4 injections of mRNA-based vaccination to prevent COVID-19 months to a year from the last vaccine boost, and we found numerous SARS-CoV-2 ...spike-specific regulatory T cell (Treg) that developed T cell memory as effector memory T cells (T
) and central memory T cells (T
). CD4+ CD25
Treg expressed the chemokine receptor CCR6 in a considerable percentage, suggesting T cell homing to the vascular endothelium, lung and gut epithelial cells and brain. Treg phenotype was different than peripherally-induced Treg (pTreg) that revert from pro-inflammatory T cells under repeated stimulatory conditions, suggesting that SARS-CoV-2 spike-specific Treg differentiated from naïve T cells in tissues where the SARS-CoV-2 spike proteins were synthetized. Twenty two of 22 subjects studied responded to vaccination developing a spike-specific CD4+ T helper (Th)1 response, and 20 of 22 developing a spike-specific CD8+ cytotoxic T cells (CTL) response. However, in vaccine recipients the expansion of spike-specific pro-inflammatory T cells was less significant than the expansion of spike-specific Treg. Effector (T
) and central memory (T
) Treg were numerous as early as after two vaccine doses, with no significant differences following additional vaccine boosts. In co-culture experiments under stimulatory conditions, Treg regulated naïve T cell differentiation toward a pro-inflammatory phenotype and suppressed interferon (IFN)γ production by SARS-CoV-2-specific CD4 + Th1 cells.
Antidrug antibody (ADA) responses impact drug safety, potency, and efficacy. It is generally assumed that ADA responses are associated with human leukocyte antigen (HLA) class II-restricted CD4+ ...T-cell reactivity. Although this review does not address ADA responses
, the analysis presented here is relevant to the topic, because measuring or predicting CD4+ T-cell reactivity is a common strategy to address ADA and immunogenicity concerns. Because human CD4+ T-cell reactivity relies on the recognition of peptides bound to HLA class II, prediction, or measurement of the capacity of different peptides to bind or be natural ligands of HLA class II is used as a predictor of CD4+ T-cell reactivity and ADA development. Thus, three different interconnected variables are commonly utilized in predicting T-cell reactivity: major histocompatibility complex (MHC) binding, capacity to be generated as natural HLA ligands, and T-cell immunogenicity. To provide the scientific community with guidance in the relative merit of different approaches, it is necessary to clearly define what outcomes are being considered. Thus, the accuracy of HLA binding predictions varies as a function of what the outcome predicted is, whether it is binding itself, natural processing, or T-cell immunogenicity. Furthermore, it is necessary that the accuracy of prediction is based on rigorous benchmarking, grounded by fair, objective, transparent, and experimental criteria. In this review, we provide our perspective on how different variables and methodologies predict each of the various outcomes and point out knowledge gaps and areas to be addressed by further experimental work.
Knowledge of aging biology needs to be expanded due to the continuously growing number of elderly people worldwide. Aging induces changes that affect all systems of the body. The risk of ...cardiovascular disease and cancer increases with age. In particular, the age-induced adaptation of the immune system causes a greater susceptibility to infections and contributes to the inability to control pathogen growth and immune-mediated tissue damage. Since the impact of aging on immune function, is still to be fully elucidated, this review addresses some of the recent understanding of age-related changes affecting key components of immunity. The emphasis is on immunosenescence and inflammaging that are impacted by common infectious diseases that are characterized by a high mortality, and includes COVID-19, HIV and tuberculosis.
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