scholarly journals SARS-CoV-2 Proteome-Wide Analysis Revealed Significant Epitope Signatures in COVID-19 Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Tatjana Schwarz ◽  
Kirsten Heiss ◽  
Yuvaraj Mahendran ◽  
Fiordiligie Casilag ◽  
Florian Kurth ◽  
...  
Keyword(s):  
Viral Infections ◽  
Severe Disease ◽  
Severe Pneumonia ◽  
Asymptomatic Infection ◽  
Disease Outcome ◽  
Humoral Immune ◽  
Peptide Microarrays ◽  
Humoral Immune Responses ◽  
Longitudinal Approach ◽  
Humoral Responses

The WHO declared the COVID-19 outbreak a public health emergency of international concern. The causative agent of this acute respiratory disease is a newly emerged coronavirus, named SARS-CoV-2, which originated in China in late 2019. Exposure to SARS−CoV−2 leads to multifaceted disease outcomes from asymptomatic infection to severe pneumonia, acute respiratory distress and potentially death. Understanding the host immune response is crucial for the development of interventional strategies. Humoral responses play an important role in defending viral infections and are therefore of particular interest. With the aim to resolve SARS-CoV-2-specific humoral immune responses at the epitope level, we screened clinically well-characterized sera from COVID-19 patients with mild and severe disease outcome using high-density peptide microarrays covering the entire proteome of SARS-CoV-2. Moreover, we determined the longevity of epitope-specific antibody responses in a longitudinal approach. Here we present IgG and IgA-specific epitope signatures from COVID-19 patients, which may serve as discriminating prognostic or predictive markers for disease outcome and/or could be relevant for intervention strategies.

scholarly journals Purified Hexameric Epstein-Barr Virus-Encoded BARF1 Protein for Measuring Anti-BARF1 Antibody Responses in Nasopharyngeal Carcinoma Patients

2010 ◽  
Vol 18 (2) ◽  
pp. 298-304 ◽  
Author(s):  
E. K. Hoebe ◽  
S. H. Hutajulu ◽  
J. van Beek ◽  
S. J. Stevens ◽  
D. K. Paramita ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Antibody Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Humoral Immune ◽  
Barr Virus ◽  
Humoral Immune Responses ◽  
Human Sera ◽  
Epstein Barr ◽  
Humoral Responses

ABSTRACTWHO type III nasopharyngeal carcinoma (NPC) is highly prevalent in Indonesia and 100% associated with Epstein-Barr virus (EBV). NPC tumor cells express viral proteins, including BARF1, which is secreted and is considered to have oncogenic and immune-modulating properties. Recently, we found conserved mutations in the BARF1 gene in NPC isolates. This study describes the expression and purification of NPC-derived BARF1 and analyzes humoral immune responses against prototype BARF1 (B95-8) and purified native hexameric BARF1 in sera of Indonesian NPC patients (n= 155) compared to healthy EBV-positive (n= 56) and EBV-negative (n= 16) individuals. BARF1 (B95-8) expressed inEscherichia coliand baculovirus, as well as BARF1-derived peptides, did not react with IgG or IgA antibodies in NPC. Purified native hexameric BARF1 protein isolated from culture medium was used in enzyme-linked immunosorbent assay (ELISA) and revealed relatively weak IgG and IgA responses in human sera, although it had strong antibody responses to other EBV proteins. Higher IgG reactivity was found in NPC patients (P= 0.015) than in regional Indonesian controls or EBV-negative individuals (P< 0.001). IgA responses to native BARF1 were marginal. NPC sera with the highest IgG responses to hexameric BARF1 in ELISA showed detectable reactivity with denatured BARF1 by immunoblotting. In conclusion, BARF1 has low immunogenicity for humoral responses and requires native conformation for antibody binding. The presence of antibodies against native BARF1 in the blood of NPC patients provides evidence that the protein is expressed and secreted as a hexameric protein in NPC patients.

scholarly journals Titers of Neutralizing Antibodies against SARS-CoV-2 Are Independent of Symptoms of Non-Severe COVID-19 in Young Adults

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 284
Author(s):  
Hulda R. Jonsdottir ◽  
Michel Bielecki ◽  
Denise Siegrist ◽  
Thomas W. Buehrer ◽  
Roland Züst ◽  
...  
Keyword(s):  
Young Adults ◽  
Neutralizing Antibodies ◽  
Severe Disease ◽  
Humoral Response ◽  
Neutralizing Antibody ◽  
Neutralization Assay ◽  
Asymptomatic Infection ◽  
Homogeneous Population ◽  
Humoral Immune ◽  
Antibody Titers

Neutralizing antibodies are an important part of the humoral immune response to SARS-CoV-2. It is currently unclear to what extent such antibodies are produced after non-severe disease or asymptomatic infection. We studied a cluster of SARS-CoV-2 infections among a homogeneous population of 332 predominantly male Swiss soldiers and determined the neutralizing antibody response with a serum neutralization assay using a recombinant SARS-CoV-2-GFP. All patients with non-severe COVID-19 showed a swift humoral response within two weeks after the onset of symptoms, which remained stable for the duration of the study. One month after the outbreak, titers in COVID-19 convalescents did not differ from the titers of asymptomatically infected individuals. Furthermore, symptoms of COVID-19 did not correlate with neutralizing antibody titers. Therefore, we conclude that asymptomatic infection can induce the same humoral immunity as non-severe COVID-19 in young adults.

scholarly journals Simulation Model for Dynamics of Dengue with Innate and Humoral Immune Responses

2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
S. D. Perera ◽  
S. S. N. Perera
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Dengue Virus ◽  
Dengue Infection ◽  
Asymptomatic Infection ◽  
Severe Dengue ◽  
Viral Kinetics ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Kinetics Of

Dengue virus is a mosquito borne Flavivirus and the most prevalent arbovirus in tropical and subtropical regions around the world. The incidence of dengue has increased drastically over the last few years at an alarming rate. The clinical manifestation of dengue ranges from asymptomatic infection to severe dengue. Even though the viral kinetics of dengue infection is lacking, innate immune response and humoral immune response are thought to play a major role in controlling the virus count. Here, we developed a computer simulation mathematical model including both innate and adaptive immune responses to study the within-host dynamics of dengue virus infection. A sensitivity analysis was carried out to identify key parameters that would contribute towards severe dengue. A detailed stability analysis was carried out to identify relevant range of parameters that contributes to different outcomes of the infection. This study provides a qualitative understanding of the biological factors that can explain the viral kinetics during a dengue infection.

scholarly journals Targeted Inactivation of the Tetraspanin CD37 Impairs T-Cell-Dependent B-Cell Response under Suboptimal Costimulatory Conditions

2000 ◽  
Vol 20 (15) ◽  
pp. 5363-5369 ◽  
Author(s):  
Klaus-Peter Knobeloch ◽  
Mark D. Wright ◽  
Adrian F. Ochsenbein ◽  
Oliver Liesenfeld ◽  
Jürgen Löhler ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Viral Infections ◽  
Cell Interactions ◽  
Antibody Responses ◽  
Cellular Activation ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Targeted Inactivation ◽  
Deficient Mice

ABSTRACT CD37 is a membrane protein of the tetraspanin superfamily, which includes CD9, CD53, CD63, CD81, and CD82. Many of these molecules are expressed on leukocytes and have been implicated in signal transduction, cell-cell interactions, and cellular activation and development. We generated and analyzed mice deficient for CD37. Despite the high expression of CD37 on cells of the immune system, no changes in development and cellular composition of lymphoid organs were observed in mice lacking CD37. Analyses of humoral immune responses revealed a reduced level of immunoglobulin G1 (IgG1) in the sera of nonimmunized mice and an alteration of responses to T-cell-dependent antigens. Antibody responses to model antigen administered in the absence of adjuvant and to viral infections were generally poor in CD37-deficient mice. These poor antibody responses could be overcome by the immunization of antigen together with adjuvant. These results suggest a role for CD37 in T-cell–B-cell interactions which manifests itself under suboptimal costimulatory conditions.

scholarly journals Dynamic Alterations of Anti-S-Protein Igg Subclasses and of Th1/Th2 Responses are Hallmarks of Acute Severe COVID-19 Disease

2021 ◽  
Author(s):  
Yun Shan Goh ◽  
Siew-Wai Fong ◽  
Siti Naqiah Amrun ◽  
Cheryl Lee ◽  
Pei Xiang Hor ◽  
...  
Keyword(s):  
Disease Severity ◽  
Severe Disease ◽  
Th2 Response ◽  
S Protein ◽  
Th1 Response ◽  
Humoral Immune ◽  
Mild Disease ◽  
Humoral Immune Responses ◽  
Disease Spectrum ◽  
Antibody Levels

Abstract PurposeCOVID-19, caused by Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), has a wide disease spectrum ranging from asymptomatic to severe. While it is widely accepted that specific humoral immune responses are critical in controlling the infection, the relationship between the humoral immune response and disease severity is currently unclear.MethodsUsing a flow cytometry-based assay to detect specific antibodies against full length S protein, we compared the antibody levels between patients from different severity groups. We also analysed the cytokine profiles of patients from different severity groups by multiplex microbead-based immunoassay.ResultsWe found an association between specific IgM, IgA and IgG against the spike protein and disease severity. By comparing the ratio of Th1 IgG1 and IgG3 to Th2 IgG2 and IgG4, we observed that all severity groups exhibited a ratio that was skewed towards a stronger Th1 response over Th2 response. In addition to the strong Th1 response, patients with severe disease also developed a Th2 response, as exemplified by the smaller ratio of IgG1 and IgG3 over IgG2 and IgG4 and the smaller Th1/Th2 cytokine ratios, compared to patients with mild disease severity. ConclusionThe results suggest that acute severity or disease resolution is associated with a specific immunological phenotype. A smaller skew towards a Th1 response over Th2 response, during infection, may contribute to disease progression, while a greater skew towards a Th1 response over Th2 response may contribute to a better disease outcome. This may suggest potential therapeutic approaches to COVID-19 disease management.

scholarly journals Humoral protection to SARS-CoV2 declines faster in patients on TNF alpha blocking therapies

RMD Open ◽  
2021 ◽  
Vol 7 (3) ◽  
pp. e002008
Author(s):  
Ulf M Geisen ◽  
Melike Sümbül ◽  
Florian Tran ◽  
Dennis K Berner ◽  
Hayley M Reid ◽  
...  
Keyword(s):  
T Cell ◽  
Neutralizing Antibodies ◽  
Inflammatory Diseases ◽  
Cd4 T Cell ◽  
Vulnerable Groups ◽  
Humoral Immune ◽  
Vaccine Responses ◽  
Humoral Immune Responses ◽  
Disease Modifying ◽  
Humoral Responses

BackgroundThe persistence of the SARS-CoV2 pandemic, partly due to the appearance of highly infectious variants, has made booster vaccinations necessary for vulnerable groups. Questions remain as to which cohorts require SARS-CoV2 boosters. However, there is a critical lack of data on the dynamics of vaccine responses in patients with chronic inflammatory diseases (CID) undergoing immunosuppressive/disease modifying anti-rheumatic (DMARD) treatment. Here, we present the first data regarding the decline of the vaccine-induced humoral immune responses in patients with CID.Methods23 patients with CID were monitored clinically and for anti-spike IgG and IgA levels, neutralization efficacy and antigen-specific CD4+ T cell responses over the first 6 months after SARS-CoV2 vaccination. 24 healthy individuals were included as controls.ResultsWhile anti-spike IgG-levels declined in CID patients and healthy controls, patients receiving anti-TNF treatment showed significantly greater declines at 6 months post second vaccination in IgG and especially neutralizing antibodies. IgA levels were generally lower in CID patients, particularly during anti-TNF therapy. No differences in SARS-CoV2 spike-specific CD4+ T-cell frequencies were detected.ConclusionAlthough the long-term efficacy of SARS-CoV2 vaccination in CID patients undergoing disease-modifying therapy is still not known, the pronounced declines in humoral responses towards SARS-CoV2 6 months after mRNA vaccination in the context of TNF blockade should be considered when formulating booster regimens. These patients should be considered for early booster vaccinations.

scholarly journals Autoantibodies in COVID-19 correlate with anti-viral humoral responses and distinct immune signatures

2022 ◽  
Author(s):  
Patrick Taeschler ◽  
Carlo Cervia ◽  
Yves Zurbuchen ◽  
Sara Hasler ◽  
Christian Pou ◽  
...  
Keyword(s):  
Indirect Immunofluorescence ◽  
Autoantibody Production ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Serum Proteomics ◽  
Immune Signatures ◽  
Autoimmune Pathology ◽  
Highly Sensitive ◽  
One Year ◽  
Humoral Responses

Background: Several autoimmune features occur during coronavirus disease 2019 (COVID-19), with possible implications for disease course, immunity, and autoimmune pathology. Objective: We longitudinally screened for clinically relevant systemic autoantibodies to assess their prevalence, temporal trajectory, and association with immunity, comorbidities, and severity of COVID-19. Methods: We performed highly sensitive indirect immunofluorescence assays to detect anti-nuclear antibodies (ANA) and anti-neutrophil cytoplasmic antibodies (ANCA), along with serum proteomics and virome-wide serological profiling in a multicentric cohort of 175 COVID-19 patients followed-up to one year after infection, eleven vaccinated individuals, and 41 unexposed controls. Results: Compared to healthy controls, similar prevalence and patterns of ANA were present in patients during acute COVID-19 and recovery. However, paired analysis revealed a subgroup of patients with transient presence of certain ANA patterns during acute COVID-19. Furthermore, patients with severe COVID-19 exhibited a high prevalence of ANCA during acute disease. These autoantibodies were quantitatively associated with higher SARS-CoV-2-specific antibody titers in COVID-19 patients and in vaccinated individuals, thus linking autoantibody production to increased antigen-specific humoral responses. Notably, the qualitative breadth of antibodies cross-reactive with other coronaviruses was comparable in ANA-positive and ANA-negative individuals during acute COVID-19. In autoantibody-positive patients, multiparametric characterization demonstrated an inflammatory signature during acute COVID-19 and alterations of the B cell compartment after recovery. Conclusion: Highly sensitive indirect immunofluorescence assays revealed transient autoantibody production during acute SARS-CoV-2 infection, while the presence of autoantibodies in COVID-19 patients correlated with increased anti-viral humoral immune responses and inflammatory immune signatures.

scholarly journals Overcoming Immunity to a Viral Vaccine by DNA Priming before Vector Boosting

2003 ◽  
Vol 77 (1) ◽  
pp. 799-803 ◽  
Author(s):  
Zhi-yong Yang ◽  
Linda S. Wyatt ◽  
Wing-pui Kong ◽  
Zoe Moodie ◽  
Bernard Moss ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Vectors ◽  
Ebola Virus ◽  
Viral Vector ◽  
Hemorrhagic Fever ◽  
Viral Immunity ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Viral Vaccine ◽  
Humoral Responses

ABSTRACT Replication-defective adenovirus (ADV) and poxvirus vectors have shown potential as vaccines for pathogens such as Ebola or human immunodeficiency virus in nonhuman primates, but prior immunity to the viral vector in humans may limit their clinical efficacy. To overcome this limitation, the effect of prior viral exposure on immune responses to Ebola virus glycoprotein (GP), shown previously to protect against lethal hemorrhagic fever in animals, was studied. Prior exposure to ADV substantially reduced the cellular and humoral immune responses to GP expressed by ADV, while exposure to vaccinia inhibited vaccine-induced cellular but not humoral responses to GP expressed by vaccinia. This inhibition was largely overcome by priming with a DNA expression vector before boosting with the viral vector. Though heterologous viral vectors for priming and boosting can also overcome this effect, the paucity of such clinical viral vectors may limit their use. In summary, it is possible to counteract prior viral immunity by priming with a nonviral, DNA vaccine.

scholarly journals Ehrlichia chaffeensis Infections in Drosophila melanogaster

2009 ◽  
Vol 77 (11) ◽  
pp. 4815-4826 ◽  
Author(s):  
Alison Luce-Fedrow ◽  
Tonia Von Ohlen ◽  
Stephen K. Chapes
Keyword(s):  
Drosophila Melanogaster ◽  
Amblyomma Americanum ◽  
Immune Defense ◽  
Ehrlichia Chaffeensis ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Defense Induction ◽  
Humoral Responses ◽  
Human Monocytic Ehrlichiosis

ABSTRACT Ehrlichia chaffeensis is an obligate, intracellular bacterium, transmitted by the tick Amblyomma americanum, and is the causative agent of human monocytic ehrlichiosis infections. We previously demonstrated that E. chaffeensis is capable of growing in Drosophila S2 cells. Therefore, we tested the hypothesis that E. chaffeensis can infect adult Drosophila melanogaster. Adult Drosophila organisms were experimentally challenged with intra-abdominal injections of bacteria. Ehrlichia-infected flies showed decreased survival compared to wild-type flies, and bacteria isolated from flies could reinfect mammalian macrophages. Ehrlichia infections activated both the cellular and humoral immune responses in the fly. Hemocytes phagocytosed bacteria after injection, and antimicrobial peptide pathways were induced following infection. Increased pathogenicity in flies carrying mutations in genes in both the Toll and Imd pathways suggests that both immune defense pathways participate in host defense. Induction of Drosophila cellular and humoral responses and the in vivo replication of E. chaffeensis suggests that D. melanogaster is a suitable host for E. chaffeensis. In the future, it will be a useful tool to unlock some of the in vivo mysteries of this arthropod-borne bacterium.

scholarly journals Humoral Immune Responses against the Mycobacteriumtuberculosis 38-Kilodalton, MTB48, and CFP-10/ESAT-6 Antigens in Tuberculosis

2010 ◽  
Vol 17 (3) ◽  
pp. 372-375 ◽  
Author(s):  
Xueqiong Wu ◽  
Yourong Yang ◽  
Junxian Zhang ◽  
Bangying Li ◽  
Yan Liang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Healthy Subjects ◽  
Enzyme Linked Immunosorbent Assay ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Single Antigen ◽  
Human Sera ◽  
Low Sensitivity ◽  
Humoral Responses ◽  
Culture Negative

ABSTRACT The diagnosis of smear-negative and culture-negative patients with active tuberculosis (TB) is challenging. The detection of Mycobacterium tuberculosis-specific antibodies in human sera has been an important diagnostic aid. However, detection of antibody responses to a single antigen usually has a low sensitivity for diagnosis of TB. In this study, humoral immune responses against recombinant M. tuberculosis 38-kDa, MTB48, and CFP-10/ESAT-6 (culture filtrate protein 10/6-kDa early secreted antigen target of M. tuberculosis) antigens in 250 Chinese TB patients and 260 healthy subjects were evaluated by an enzyme-linked immunosorbent assay (ELISA). The levels of antibodies against those antigens in TB patients, even in bacterium-negative ones, were significantly higher than those in healthy subjects (P < 0.001). The serodiagnostic sensitivities to detect antibodies against individual antigens, i.e., recombinant M. tuberculosis 38-kDa, MTB48, and CFP-10/ESAT-6 antigens, in TB patients were 73.6%, 73.2%, and 60.4%, respectively, with specificities of 85.4%, 77.7%, and 73.8%, respectively. Importantly, the sensitivity to positively detect humoral responses to one of the antigens increased further. Our data suggest that the humoral immune responses to M. tuberculosis antigens in TB patients are heterogeneous. The 38-kDa, MTB48, and CFP-10/ESAT-6 antigens can be used as the cocktail antigens in the serodiagnosis of active TB, especially for smear- or culture-negative TB cases.

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