Vaccination with MAGE-3 Protein Can Induce a Potent Immune Response in a Healthy Donor Which Can Be Adoptively Transferred Via Stem Cell Transplant (Tx) to a Multiple Myeloma (MM) Patient.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2197-2197 ◽  
Author(s):  
Sacha Gnjatic ◽  
Susann Szmania ◽  
Amberly Moreno ◽  
M. Cottler-Fox ◽  
John Shaughnessy ◽  
...  
Keyword(s):  
Stem Cells ◽  
Immune Response ◽  
Humoral Immunity ◽  
Healthy Donor ◽  
Cellular Response ◽  
Cross Reactivity ◽  
Cell Transplant ◽  
Cell Responses ◽  
Humoral Responses ◽  
First Time

Abstract A MAGE-3 positive, stage IIIA MM patient with a twin donor provided a unique opportunity to study if vaccination with MAGE-3 protein induces immune responses in the healthy twin, and if these responses can be adoptively transferred to the patient and expanded by booster vaccines. The patient was treated with MEL 200 tandem Tx (Tx1: auto, Tx2: syngeneic) and MAGE-3 recombinant protein in ASO2B adjuvant. The MAGE-3 negative, identical twin donor received 3 vaccines and was leukapheresed (LP1) one week after the 3rd vaccine to store vaccine-induced immune cells. Donor G-CSF mobilized stem cells (Tx2) were transfused fresh to the patient after MEL conditioning. Donor LP1 was transfused to the patient 21 days post Tx2 and followed by 8 booster vaccines. The donor continued vaccinations and LP2 was collected one week after the 8th vaccine and transfused to the patient who had received 4 of 8 planned booster vaccines. Ab responses to MAGE-3 and controls NY-ESO-1, LAGE-1, MAGE-1, MAGE-4, and p-53 were assessed by ELISA. MAGE-3 specific CD8+ T-cell responses to autologous EBV transformed cells pulsed with pooled 20-mer overlapping peptides from MAGE-3 were assessed by ELISPOT. Neither twin had pre-existing anti-MAGE-3 humoral immunity. The donor twin developed MAGE-3 ab up to 1/6400. The patient had a detectable anti-MAGE-3 titer post donor Tx2 (1/400) which was boosted by subsequent vaccinations (1/1600). After the transfer of LP2 and vaccines 5–8, the patient had MAGE-3 ab titers similar to those in the donor. There was low but significant cross-reactivity only to MAGE-4. A vaccine-induced CD8+ cellular response to a previously undescribed MAGE-3115–123, HLA-A68 restricted epitope was observed in the donor and patient. MAGE-3115–123 is in the same region as (but is distinct from) two other known HLA-A2 and -B40 epitopes. Further studies with recombinant MAGE-3 protein and tetramers are in progress to study if this epitope is indeed naturally processed and presented. The patient is in CR nearly 1 yr post Tx2. We show for the first time that vaccinating a healthy donor with a defined cancer-testis antigen can induce both cellular and humoral responses and that such responses can be transferred and expanded post Tx in the recipient. Close inspection of the ab curves shows that humoral immunity was transferred with the donor stem cells (Tx2) and expanded in the patient by further booster vaccines. We could not establish with certainty that LP1 and LP2 contributed further to transferring humoral or cellular immunity. It is hoped that this approach may be used to induce a specific anti-MM immune response after autologous or allogeneic Tx and reduce MM relapse. Figure Figure

scholarly journals Human Papillomavirus Type 16 E7 Peptide-Directed CD8+ T Cells from Patients with Cervical Cancer Are Cross-Reactive with the Coronavirus NS2 Protein

2003 ◽  
Vol 77 (9) ◽  
pp. 5464-5474 ◽  
Author(s):  
Katja Nilges ◽  
Hanni Höhn ◽  
Henryk Pilch ◽  
Claudia Neukirch ◽  
Kirsten Freitag ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Immune Response ◽  
T Cells ◽  
Human Papillomavirus ◽  
T Cell ◽  
T Cell Responses ◽  
Cross Reactivity ◽  
Antiviral Immune Response ◽  
Human Papillomavirus Type 16 ◽  
Cell Responses

ABSTRACT Human papillomavirus type 16 (HPV16) E6 and E7 oncoproteins are required for cellular transformation and represent candidate targets for HPV-specific and major histocompatibility complex class I-restricted CD8+-T-cell responses in patients with cervical cancer. Recent evidence suggests that cross-reactivity represents the inherent nature of the T-cell repertoire. We identified HLA-A2 binding HPV16 E7 variant peptides from human, bacterial, or viral origin which are able to drive CD8+-T-cell responses directed against wild-type HPV16 E7 amino acid 11 to 19/20 (E711-19/20) epitope YMLDLQPET(T) in vitro. CD8+ T cells reacting to the HLA-A2-presented peptide from HPV16 E711-19(20) recognized also the HLA-A2 binding peptide TMLDIQPED (amino acids 52 to 60) from the human coronavirus OC43 NS2 gene product. Establishment of coronavirus NS2-specific, HLA-A2-restricted CD8+-T-cell clones and ex vivo analysis of HPV16 E7 specific T cells obtained by HLA-A2 tetramer-guided sorting from PBL or tumor-infiltrating lymphocytes obtained from patients with cervical cancer showed that cross-reactivity with HPV16 E711-19(20) and coronavirus NS252-60 represents a common feature of this antiviral immune response defined by cytokine production. Zero of 10 patients with carcinoma in situ neoplasia and 3 of 18 patients with cervical cancer showed ≥0.1% HPV16 E7-reactive T cells in CD8+ peripheral blood lymphocytes. In vivo priming with HPV16 was confirmed in patients with cervical cancer or preinvasive HPV16-positive lesions using HLA-A2 tetramer complexes loaded with the E6-derived epitope KLPQLCTEL. In contrast, we could not detect E6-reactive T cells in healthy individuals. These data imply that the measurement of the HPV16 E711-19(20) CD8+-T-cell response may reflect cross-reactivity with a common pathogen and that variant peptides may be employed to drive an effective cellular immune response against HPV.

scholarly journals Regulatory/inflammatory cellular response discrimination in operational tolerance

2019 ◽  
Vol 34 (12) ◽  
pp. 2143-2154
Author(s):  
Priscila Carmona ◽  
Yordanka Medina-Armenteros ◽  
Amanda Cabral ◽  
Sandra Maria Monteiro ◽  
Simone Gonçalves Fonseca ◽  
...  
Keyword(s):  
Cellular Response ◽  
Interferon Γ ◽  
Cross Reactivity ◽  
Specific Response ◽  
Heat Shock Protein 60 ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Cell Responses ◽  
Operational Tolerance ◽  
Stimulating Factor

Abstract Background Antigen-specific cellular response is essential in immune tolerance. We tested whether antigen-specific cellular response is differentially modulated in operational tolerance (OT) in renal transplantation with respect to critical antigenic challenges in allotransplantation—donor antigens, pathogenic antigens and self-antigens. Methods We analysed the profile of immunoregulatory (REG) and pro-inflammatory (INFLAMMA) cytokines for the antigen-specific response directed to these three antigen groups, by Luminex. Results We showed that, in contrast to chronic rejection and healthy individuals, OT gives rise to an immunoregulatory deviation in the cellular response to donor human leucocyte antigen DR isotype peptides, while preserving the pro-inflammatory response to pathogenic peptides. Cellular autoreactivity to the N6 heat shock protein 60 (Hsp60) peptide also showed a REG profile in OT, increasing IL4, IL-5, IL-10 and IL-13. Conclusions The REG shift of donor indirect alloreactivity in OT, with inhibition of interleukin (IL)-1B, IL-8, IL-12, IL-17, granulocyte colony-stimulating factor, Interferon-γ and monocyte chemoattractant protein-1, indicates that this may be an important mechanism in OT. In addition, the differential REG profile of cellular response to the Hsp60 peptide in OT suggests that REG autoimmunity may also play a role in human transplantation tolerance. Despite cross-reactivity of antigen-specific T cell responses, a systemic functional antigen-specific discrimination takes place in OT.

Interferon α Has Varied Effects On CD34+ Cells From Patients With Polycythemia Vera

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2840-2840
Author(s):  
Min Lu ◽  
Seungyeul Yoo ◽  
Lijuan Xia ◽  
Xiaoli Wang ◽  
Yan Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Immune Response ◽  
Colony Formation ◽  
Cellular Response ◽  
P Value ◽  
Type I ◽  
Signature Genes ◽  
Cd34 Cells ◽  
Ifn Γ

Abstract Prolonged therapy with pegylated interferon a (Peg-IFNα 2a) leads to hematological and complete molecular remissions in 70% and 17% of patients with polycythemia vera (PV) , respectively (Quintas-Cardama et al, Blood 2013). We have previously shown that PV CD34+ cells are more responsive to Peg-IFNα 2a than normal CD34+ cell. The type I IFN receptor 1 and 2 were shown to be expressed by a greater number of by PV CD34+ cells than normal(N) CD34+ cells (p=0.01 and p=0.002, respectively). The effects of Peg-IFNα 2a on PV hematopoietic stem cells(HSCs) was next evaluated by incubating PV CD34+ cell for 7 days with Peg-IFNα 2a (200ng/ml) followed by their transplantation into NSG mice. The degree of human cell chimerism following the transplantation of MPN CD 34+ cells was reduced by 50 -90% and the JAK2V617F allele burden by 40 -80%. Treatment of N CD34+ cells with Peg-IFNα 2a reduced donor chimerism by only 20%. We next examined the effects of increasing doses of Peg-IFNα 2a on CD34+ cells from 11 PV patients and 5 N controls. In 4 out of 10 PV cases the IC50 of Peg-IFNα 2a was less than 200ng/ml while in the remainder of cases the IC50 was greater. Low doses of IFNa were capable of eliminating JAK2V617F+ hematopoietic colonies in these IFNα sensitive patients while higher doses of IFNα were required to achieve the same effect in the other patients. PV and N CD34+ cells were then profiled using Illumina Gene expression arrays. In total, 32 intensity data files were generated, each containing 47,231 features, corresponding to 12,388 unique genes. At p-value <0.05 386 genes were down-regulated in PV; these genes were enriched for biological processes related to immune response including the IFN-γ-mediated signaling pathway (p=0.0002), the response to IFN-gamma (p=0.004), and the cellular response to IFN-γ (p=0.0004). The 715 up-regulated genes in PV were enriched for pathways involving glycolysis (p=9.4×10-05), cellular response to stress (p=0.006), and catabolic processes. The gene expression patterns of CD34+ cells incubated with and without INFα were next analyzed. At pairwise t-test p-value <0.001, 315 genes were differentially expressed (223 up-regulated and 92 down-regulated by INFα). Up-regulated genes were enriched for INFα functions and immune response including: response to type I IFN (p=9.0×10-49), innate immune response (2.6×10-45), response to virus (7.5×10-40). Among the 223 up-regulated genes, half were previously known as IFN regulated genes (IRGs). The individual response (IR) of genes to IFN was then defined as: IRi=log (exp ressioni @IFN/exp ressioni@control) IR patterns were remarkably consistent within N samples while large inter-patient variations were observed within the PV samples. Significantly positive IRs were observed for 75 genes and negative IRs for 117 genes within PV as compared to N samples (p value<0.01). The 75 positively responsive genes to IFNa overlapped with 16 down-regulated PV signature genes (p=1.1×10-10) while the negatively responsive of genes overlapped with 41 up-regulated PV signature genes (p=2.2×10-24).These data indicate that the action of IFNa is associated with the alteration of the expression of specific PV signature genes. The varied inhibitory effect of Peg-IFNα 2a on PV colony formation was then correlated with the IR of individual genes. The IRs of OAS2 and RPS24 showed particularly high variance and were related to colony formation. OAS2 (2'-5'-oligoadenylate synthetase 2) is an INF-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response but also influences apoptosis, cell growth, differentiation and gene regulation. The IR of this gene was directly related to the inhibitory actions of IFNa (p=0.0011). By contrast, the IR of RPS24 (40S ribosomal protein S24), was inversely correlated to the IFNα response (p=0.0038). Mutations in RPS24 are associated with Diamond-Blackfan anemia. The strong correlation between the IR of these 2 genes with the inhibitory effects of IFNα suggests that their response ratio might be useful as therapeutic biomarker. These data indicate that the IFNα receptor is up-regulated in PV CD34+ cells and that IFNα treatment eliminates PV stem cells and its sensitivity against individual patient PV HSC/HPC varies. The patterns of differentially expressed genes following IFNα treatment may prove useful in determining its mechanism of action and predicting IFNα patient response. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Neutrophils control the magnitude and spread of the immune response in a thromboxane A2-mediated process

2013 ◽  
Vol 210 (2) ◽  
pp. 375-387 ◽  
Author(s):  
Chiao-Wen Yang ◽  
Emil R. Unanue
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Lymph Nodes ◽  
B Cell ◽  
Adoptive Transfer ◽  
Cellular Response ◽  
Thromboxane A2 ◽  
Cd4 T Cell ◽  
Protein Antigens ◽  
Cell Responses

Neutrophils are obligate cells entering lymph nodes shortly after immunization with protein antigens in adjuvants, starting during the first hour and continuing for several days in two distinct waves. Previously, we demonstrated the strong suppressive effects of neutrophils on CD4 T cell and B cell responses, using either neutrophil-depleting antibodies or genetically neutropenic mice. In this study, we find that neutrophils are the major cells controlling the spread of T cell responses to distal lymph nodes. Although in the presence of neutrophils, ∼75% of the response was restricted to the draining node, in their absence, most of the response was found in distal nodes. Prostanoids were responsible for the rapid entry of neutrophils into the draining nodes, as well as for the two distinct neutrophil effects: the modulation of the magnitude of the cellular response, and in its spread outside the draining nodes. Neutrophil-produced thromboxane A2 was the key eicosanoid controlling both effects. Adoptive transfer of neutrophils into mice genetically deficient in neutrophils indicated their role in both. These functions of neutrophils are important in infections and vaccinations with adjuvants where neutrophils are abundant in the initial stages.

scholarly journals DNA Immunization by Plasmodium falciparum Liver-Stage Antigen 3 Induces Protection againstPlasmodium yoelii Sporozoite Challenge

2001 ◽  
Vol 69 (2) ◽  
pp. 1202-1206 ◽  
Author(s):  
Jean-Pierre Sauzet ◽  
Blanca-Liliana Perlaza ◽  
Karima Brahimi ◽  
Pierre Daubersies ◽  
Pierre Druilhe
Keyword(s):  
Plasmodium Falciparum ◽  
Immune Responses ◽  
Plasmodium Yoelii ◽  
Cross Reactivity ◽  
Liver Stage ◽  
Cell Responses ◽  
Heterologous Challenge ◽  
High Gamma ◽  
First Time ◽  
Putative Homologue

ABSTRACT DNA-based immunization of mice by Plasmodium falciparumliver-stage antigen 3 (PfLSA3), a novel highly conserved P. falciparum preerythrocytic antigen, was evaluated. Animals developed a dominant Th1 immune response (high gamma interferon T-cell responses and predominance of immunoglobulin G2a) to each of three recombinant proteins spanning the molecule. We have exploited the immunological cross-reactivity of PfLSA3 with its putative homologue on sporozoites of the rodent parasite Plasmodium yoelii, and we show for the first time that responses induced by PfLSA3 in mice significantly protect against a heterologous challenge by P. yoelii sporozoites. These results support a significant effect of DNA-induced immune responses on preerythrocytic stages.

scholarly journals Induction of robust cellular and humoral immunity against SARS-CoV-2 after a third dose of BNT162b2 vaccine in previously unresponsive elderly

2021 ◽  
Author(s):  
Addi Romero Olmedo ◽  
Axel Schulz ◽  
Svenja Hochstäter ◽  
Dennis DasGupta ◽  
Iiris Virta ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Humoral Immunity ◽  
Specific Antibody ◽  
T Cell Responses ◽  
The Elderly ◽  
Cell Responses ◽  
Cellular And Humoral Immunity

Abstract Herein, we compared SARS-CoV-2-specific antibody and T-cell responses to two doses of BNT162b2 mRNA in 51 vaccinees > 80 years old and 46 (20–53 years old) controls. The responses of the elderly were much lower and 10% non-responders were identified. Importantly, in four of them, a third vaccination raised the immune response to levels seen in responders after two vaccinations, thus implying that non-response is not fateful even in the elderly.

scholarly journals Respon imun krustase

2014 ◽  
Vol 2 (2) ◽  
Author(s):  
Henky Manoppo ◽  
Magdalena E.F Kolopita
Keyword(s):  
Immune Response ◽  
Cellular Response ◽  
Binding Protein ◽  
Adaptive Immune System ◽  
Humoral Response ◽  
Peptidoglycan Recognition Protein ◽  
Recognition Protein ◽  
Foreign Materials ◽  
Nonspecific Immune Response ◽  
Humoral Responses

Crustacean does not have adaptive immune system and mostly depends on innate or nonspecific immune response. This system can recognize and destroy foreign materials including pathogen.  The nonspecific immune responses of crustacean consist of cellular and humoral responses.  In cellular response, hemocyte plays an important role in body defenses to pathogen including virus, bacteria, fungi, and parasites. In humoral response, recognition of pathogen is mediated by protein and enzyme such as β-1,3-glucan-binding protein (BGBP),  lipopolysaccharide-binding protein (LPS-BP), peptidoglycan recognition protein, phenoloxydase enzime. Keywords: crustacean, nonspecific immune response, cellular responses, humoral response, protein, enzime

scholarly journals Synergic coordination of stem cells is required to induce a regenerative response in anthozoan cnidarians

2019 ◽  
Author(s):  
Aldine R. Amiel ◽  
Kevin Foucher ◽  
Solène Ferreira ◽  
Eric Röttinger
Keyword(s):  
Stem Cells ◽  
Cellular Response ◽  
Body Parts ◽  
The Reformation ◽  
Slow Cycling ◽  
Structure Complexity ◽  
Stem Cell Populations ◽  
Quiescent Stem Cells ◽  
First Time ◽  
Inductive Signal

AbstractLittle is known about the origin of the inductive signal that translates the amputation stress into a cooperative cellular response. By studying the process underlying the reformation of lost body parts in the anthozoan cnidarian Nematostella vectensis, we identified a regeneration-inducing structure that, via a tissue crosstalk, is responsible for the initiation of the repair program. We further revealed for the first time in anthozoan cnidarians, that fast and slow-cycling/quiescent stem cells respond to the amputation stress and actively participate in the reformation of lost body parts. Importantly, a synergic interaction of both stem cell populations is required to complete the regeneration process. Our findings suggest that the emergence/loss of structure complexity/compartmentalization influences the proprieties of tissue plasticity, changes the competence of a tissue to reprogram and, in the context of regeneration, the capacity of the tissue to emit or respond to a regeneration-inducing signal.

scholarly journals Humoral and T Cell Immune Responses to Sars-Cov-2 Vaccination in Hematopoietic Cell Transplant Recipients

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2896-2896
Author(s):  
Eleni Gavriilaki ◽  
Anastasia Papadopoulou ◽  
Tasoula Touloumenidou ◽  
Fani Stavridou ◽  
Evdoxia Koravou ◽  
...  
Keyword(s):  
Immune Response ◽  
Clinical Trials ◽  
T Cell ◽  
Immune Responses ◽  
Research Funding ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Transplant Recipients ◽  
Hematopoietic Cell Transplant ◽  
Cell Responses

Abstract Background. Hematopoietic cell transplant (HCT) recipients who develop coronavirus disease 2019 (COVID-19), have dismal prognosis with approximately 20% mortality. Given the lack of a specific and effective therapy, the availability of various vaccination platforms against SARS-CοV-2 has generated optimism towards the development of a robust herd immunity. Notwithstanding the prioritization of HCT recipients to COVID-19 vaccination, limited information is available on whether and to what extent, they mount an immune response to SARS-CοV-2 vaccination as they were generally excluded from vaccination trials. Aim. To gain insights in the immune responses developed to SARS-CoV-2 vaccines under immunosuppression, we studied the humoral and cellular immune responses to SARS-CoV-2 vaccination in HCT recipients. Methods. We prospectively studied (April-July 2021), adult patients who had undergone HCT in our Unit and received two doses of a SARS-CoV-2 vaccine (as per international guidelines) after providing written informed consent. Responses were studied before each vaccination dose and 12-51 days later after the second dose. Neutralizing antibodies against SARS-CoV-2 (CoV-2-NAbs) were measured using an FDA approved methodology for diagnostic use (ELISA, cPass™ SARS-CoV-2 NAbs Detection Kit; GenScript, Piscataway, NJ, USA; cut-off value for a positive result set at ≥30%) and SARS-CoV-2 spike-specific T cells (spike-STs) by interferon-γ Elispot after pulsing peripheral blood mononuclear cells with spike pepmixes. Results. Humoral responses were studied on 65 patients, (50 allo-HCT/15 auto-HCT, Figure A). T cell responses were measured on 38/65 vaccinated patients (32 allo-HCT/6 auto-HCT) with a median of 3 (0.17-31) and 2 years (1.25-8) post allo- and auto-HCT respectively, and 19 healthy, unexposed vaccinees. One patient with prior COVID-19, was excluded from analysis. All patients were vaccinated with the Pfizer-BioNTech, except for 2 vaccinated with the AstraZeneca vaccine. Both CoV-2-NAbs and spike-STs were barely detectable before vaccination but could be detected in both allo- and auto-HCT patients after the first vaccination dose, reaching statistically significant increase after the second vaccination dose (p&lt;0.001 and p=0.036, respectively). Circulating spike-STs in allo-HCT recipients, although present, were lower over their counterparts in healthy volunteers (p&lt;0.001) and auto-HCT patients (p=0.080). In the latter patient cohort, the rather long period post auto-HCT (≥1.25 years for all patients) might have generated unintended bias towards elevated immune responses. The longer time post HCT in all patients was associated with increased CoV-2-NAbs and spike-STs (p=0.004 and p=0.030). Allo-HCT recipients under immunosuppression had lower levels of CoV-2-NAbs and spike-STs after the booster dose compared to patients off-treatment (Figure B and C, p&lt;0.001 and p=0.021 respectively). In particular, only 50% and 40% of patients on systemic immunosuppression reached adequate CoV-2-Nab and spike-ST levels after the second dose, as compared to 98% and 94% of immunosuppression-free patients. One allo-HCT recipient with failure to mount any immune response post booster vaccination, developed 40 days later COVID-19 infection and succumbed. The one allo-HCT recipient off treatment who did not elicit protective immune response after vaccination, was suffering from metabolic syndrome, a potentially immunosuppressive entity. Overall, there was a good correlation between humoral and T-cellular responses (p=0.013), although few cases were observed with sufficient T-cell response but no humoral reactivity and vice versa. Conclusion . Herein, we report for first time humoral and T cell responses post SARS-CoV-2 vaccination in HCT recipients. Transplant recipients not under active and intense immunosuppression at the time of vaccination may benefit significantly from COVID-19 vaccination even though these responses are blunted compared to healthy individuals. However, for the severely immunocompromised patients it seems highly unlikely that they could be protected by vaccination and for this vulnerable population, different vaccination schemes or therapeutic platforms should be developed along with collateral measures including minimal exposure and immunization of caregivers and health care providers. Figure 1 Figure 1. Disclosures Gavriilaki: Alexion, Omeros, Sanofi Corporation: Consultancy; Pfizer Corporation: Research Funding; Gilead Corporation: Honoraria. Yannaki: SANDOZ: Speakers Bureau; Gilead: Speakers Bureau; Novartis: Speakers Bureau; bluebird bio, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding. Anagnostopoulos: Abbvie: Other: clinical trials; Sanofi: Other: clinical trials ; Ocopeptides: Other: clinical trials ; GSK: Other: clinical trials; Incyte: Other: clinical trials ; Takeda: Other: clinical trials ; Amgen: Other: clinical trials ; Janssen: Other: clinical trials; novartis: Other: clinical trials; Celgene: Other: clinical trials; Roche: Other: clinical trials; Astellas: Other: clinical trials .

scholarly journals Cellular immune response to SARS-CoV-2 infection in humans: a systematic review

2020 ◽  
Author(s):  
Madhumita Shrotri ◽  
May C I van Schalkwyk ◽  
Nathan Post ◽  
Danielle Eddy ◽  
Catherine Huntley ◽  
...  
Keyword(s):  
Systematic Review ◽  
Immune Response ◽  
T Cell ◽  
Cellular Immune Response ◽  
Cellular Response ◽  
T Cell Responses ◽  
Population Level ◽  
T Cell Response ◽  
Cell Responses ◽  
Cellular Immune

Introduction Understanding the cellular immune response to SARS-CoV-2 is critical to vaccine development, epidemiological surveillance and control strategies. This systematic review critically evaluates and synthesises the relevant peer-reviewed and pre-print literature published in recent months. Methods For this systematic review, independent keyword-structured literature searches were carried out in MEDLINE, Embase and COVID-19 Primer for studies published from 01/01/2020-26/06/2020. Papers were independently screened by two researchers, with arbitration of disagreements by a third researcher. Data were independently extracted into a pre-designed Excel template and studies critically appraised using a modified version of the MetaQAT tool, with resolution of disagreements by consensus. Findings were narratively synthesised. Results 61 articles were included. Almost all studies used observational designs, were hospital-based, and the majority had important limitations. Symptomatic adult COVID-19 cases consistently show peripheral T cell lymphopenia, which positively correlates with increased disease severity, duration of RNA positivity, and non-survival; while asymptomatic and paediatric cases display preserved counts. People with severe or critical disease generally develop more robust, virus-specific T cell responses. T cell memory and effector function has been demonstrated against multiple viral epitopes, and, cross-reactive T cell responses have been demonstrated in unexposed and uninfected adults, but the significance for protection and susceptibility, respectively, remains unclear. Interpretation A complex pattern of T cell response to SARS-CoV-2 infection has been demonstrated, but inferences regarding population level immunity are hampered by significant methodological limitations and heterogeneity between studies. In contrast to antibody responses, population-level surveillance of the cellular response is unlikely to be feasible in the near term. Focused evaluation in specific sub-groups, including vaccine recipients, should be prioritised.

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