scholarly journals Impaired Antibody-Dependent Cellular Cytotoxicity in a Spanish Cohort of Patients With COVID-19 Admitted to the ICU

2021 ◽  
Vol 12 ◽  
Author(s):  
Lorena Vigón ◽  
Javier García-Pérez ◽  
Sara Rodríguez-Mora ◽  
Montserrat Torres ◽  
Elena Mateos ◽  
...  
Keyword(s):  
Immune Response ◽  
Severe Disease ◽  
Potential Contribution ◽  
Humoral Immune ◽  
Dependent Cell ◽  
Critical Patients ◽  
With Memory ◽  
Neutralization Ability ◽  
Ebv Viremia ◽  
Spanish Cohort

SARS-CoV-2 infection causes COVID-19, ranging from mild to critical disease in symptomatic subjects. It is essential to better understand the immunologic responses occurring in patients with the most severe outcomes. In this study, parameters related to the humoral immune response elicited against SARS-CoV-2 were analysed in 61 patients with different presentations of COVID-19 who were recruited in Hospitals and Primary Healthcare Centres in Madrid, Spain, during the first pandemic peak between April and June 2020. Subjects were allocated as mild patients without hospitalization, severe patients hospitalized or critical patients requiring ICU assistance. Critical patients showed significantly enhanced levels of B cells with memory and plasmablast phenotypes, as well as higher levels of antibodies against SARS-CoV-2 with neutralization ability, which were particularly increased in male gender. Despite all this, antibody-dependent cell-mediated cytotoxicity was defective in these individuals. Besides, patients with critical COVID-19 also showed increased IgG levels against herpesvirus such as CMV, EBV, HSV-1 and VZV, as well as detectable CMV and EBV viremia in plasma. Altogether, these results suggest an enhanced but ineffectual immune response in patients with critical COVID-19 that allowed latent herpesvirus reactivation. These findings should be considered during the clinical management of these patients due to the potential contribution to the most severe disease during SARS-CoV-2 infection.

scholarly journals SARS-CoV-2 Infection in Fully Vaccinated Individuals of Old Age Strongly Boosts the Humoral Immune Response

2021 ◽  
Vol 8 ◽  
Author(s):  
Lisa Müller ◽  
Marcel Andrée ◽  
Philipp Niklas Ostermann ◽  
Nathalie Jazmati ◽  
Greta Flüh ◽  
...  
Keyword(s):  
Immune Response ◽  
Nursing Home ◽  
Old Age ◽  
Humoral Immune Response ◽  
Severe Disease ◽  
High Titre ◽  
Local Health Authority ◽  
Local Health ◽  
Humoral Immune ◽  
Mild Disease

Prophylactic vaccination against SARS-CoV-2 is one of the most important measures to contain the COVID-19 pandemic. Recently, break-through infections following vaccination against this virus have been reported. Here, we describe the humoral immune response of break-through infections in fully vaccinated individuals of old age from an outbreak in a nursing home. In cooperation with the local health authority, blood samples from fully vaccinated and infected as well as fully vaccinated and uninfected residents of the nursing home were collected 4 weeks after the onset of the outbreak. The humoral immune response was determined in a neutralisation assay with replication-competent virus isolates and by a quantitative ELISA. In this outbreak a total of 23 residents and four health care workers were tested positive for SARS-CoV-2. Four residents were unvaccinated, including one with a severe course of disease who later severe disease course who later succumbed to infection. Despite their old age, all vaccinated residents showed no or only mild disease. Comparison of the humoral immune response revealed significantly higher antibody levels in fully vaccinated infected individuals compared to fully vaccinated uninfected individuals (p < 0.001). Notably, although only a minority of the vaccinated uninfected group showed neutralisation capacity against SARS-CoV-2, all vaccinated and infected individuals showed high-titre neutralisation of SARS-CoV-2 including the alpha and beta variant. Large SARS-CoV-2 outbreaks can occur in fully vaccinated populations, but seem to associate with mild disease. SARS-CoV-2 infection in fully vaccinated individuals is a strong booster of the humoral immune response providing enhanced neutralisation capacity against immune evasion variants.

scholarly journals Age, Disease Severity and Ethnicity Influence Humoral Responses in a Multi-Ethnic COVID-19 Cohort

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 786
Author(s):  
Muneerah Smith ◽  
Houari B. Abdesselem ◽  
Michelle Mullins ◽  
Ti-Myen Tan ◽  
Andrew J. M. Nel ◽  
...  
Keyword(s):  
Immune Response ◽  
Disease Severity ◽  
Humoral Immune Response ◽  
Nucleocapsid Protein ◽  
Natural Infection ◽  
Severe Disease ◽  
Humoral Response ◽  
Humoral Immune ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions

The COVID-19 pandemic has affected all individuals across the globe in some way. Despite large numbers of reported seroprevalence studies, there remains a limited understanding of how the magnitude and epitope utilization of the humoral immune response to SARS-CoV-2 viral anti-gens varies within populations following natural infection. Here, we designed a quantitative, multi-epitope protein microarray comprising various nucleocapsid protein structural motifs, including two structural domains and three intrinsically disordered regions. Quantitative data from the microarray provided complete differentiation between cases and pre-pandemic controls (100% sensitivity and specificity) in a case-control cohort (n = 100). We then assessed the influence of disease severity, age, and ethnicity on the strength and breadth of the humoral response in a multi-ethnic cohort (n = 138). As expected, patients with severe disease showed significantly higher antibody titers and interestingly also had significantly broader epitope coverage. A significant increase in antibody titer and epitope coverage was observed with increasing age, in both mild and severe disease, which is promising for vaccine efficacy in older individuals. Additionally, we observed significant differences in the breadth and strength of the humoral immune response in relation to ethnicity, which may reflect differences in genetic and lifestyle factors. Furthermore, our data enabled localization of the immuno-dominant epitope to the C-terminal structural domain of the viral nucleocapsid protein in two independent cohorts. Overall, we have designed, validated, and tested an advanced serological assay that enables accurate quantitation of the humoral response post natural infection and that has revealed unexpected differences in the magnitude and epitope utilization within a population.

scholarly journals Significant control of Zika infection in macaques depends on the elapsing time after dengue exposure

2019 ◽  
Author(s):  
Crisanta Serrano-Collazo ◽  
Erick X. Pérez-Guzmán ◽  
Petraleigh Pantoja ◽  
Mariah A. Hassert ◽  
Idia V. Rodríguez ◽  
...  
Keyword(s):  
Immune Response ◽  
Neutralizing Antibodies ◽  
Severe Disease ◽  
Denv Infection ◽  
Effector Memory ◽  
Zikv Infection ◽  
Humoral Immune ◽  
Significant Control

AbstractPrior exposure to a single serotype of dengue virus (DENV) predisposes individuals to severe disease upon secondary heterologous DENV infection. Here we show that the length of time between DENV/Zika (ZIKV) infections has a qualitative impact on controlling ZIKV replication. We identified limited but significant differences in the magnitude of the early humoral immune response associated with a period of twelve months but not three months of DENV convalescence. However, their role limiting ZIKV replication is not conclusive. There was no evidence of in vivo antibody-dependent amplification of ZIKV by DENV immunity in any group. We are also showing that the significant differences among groups may be linked to a pre-existing polyfunctional CD4+ T cells response (increased IFN-g and Cd107a before ZIKV infection) and to an early and continuous expansion of the CD4+ effector memory cells early on after ZIKV infection. Those significant differences were associated with a period of 12 months after DENV infection that were not observed in a span of 3-months. These results suggest that there is a window of optimal cross-protection between ZIKV and DENV with significant consequences. These results have pivotal implications while interpreting ZIKV pathogenesis in flavivirus-experimented populations, diagnostic results interpretation and vaccine designs among others.Author SummarySince its introduction in the Americas region ZIKV virus has been associated to severe birth defects. One of the questions that remains open is the role of previous dengue or any other flavivirus immunity in the pathogenesis of ZIKV and more important, if the time elapse between DENV and ZIKV play a role enhancing ZIKV pathogenesis as it is the case for subsequent DENV infections. On this work, using NHP as a model we compared the effect of a period of 12 months vs. a period of 3 months of DENV immunity in the outcome of ZIKV infection. We found that previous DENV infection, at any of the tested period of time do not induce ZIKV enhancement. More relevant are showing that when the two infection occurs at least one year apart the preexisting DENV immunity is better at controlling ZIKV replication and that the role of the neutralizing antibodies is very limited. On the contrary our results suggest that early after ZIKV infection the cellular immune response, may plays a predominant role. Our findings have critical relevance to understand the dynamic interaction between these two flavivirus, their pathogenies, diagnosis and vaccine design.

Immune Response in Rabbits to Surface Components of Extracellular and Intracellular Forms of Vaccinia Virus

1980 ◽  
Vol 29 (3) ◽  
pp. 846-852
Author(s):  
N. Balachandran ◽  
P. Seth ◽  
L. N. Mohapatra
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Peripheral Blood ◽  
Surface Proteins ◽  
Migration Inhibition ◽  
Live Virus ◽  
Humoral Immune ◽  
Dependent Cell ◽  
Lymphocyte Cytotoxicity ◽  
Infected Cells

The development of cellular as well as humoral immune response to extracellular and intracellular forms of vaccinia virus (ECV and ICV, respectively) and their surface antigens were studied in rabbits. Direct lymphocyte cytotoxicity and peripheral blood leukocyte migration inhibition tests were used to measure cell-mediated immune response, while neutralizing and hemagglutination-inhibiting antibodies were assayed for measuring humoral immune response. Direct cytotoxicity of lymphocytes from rabbits immunized with ECV or its surface proteins was demonstrable by day 7 after immunization, and by the end of week 3 it almost declined to pre-immunization levels. Inoculation with ICV or its surface proteins failed to induce lymphocyte cytotoxicity. In contrast, migration inhibition of peripheral blood leukocytes from rabbits immunized with ECV, ICV, or their surface proteins was observed with homologous antigens. However, leukocytes from rabbits immunized with ECV or its surface proteins also showed migration inhibition in the presence of ICV. Similarly, in the humoral immune response, neutralizing antibodies were produced against homologous as well as heterologous forms of virus despite immunization with purified preparations of ECV, ICV, or their surface proteins. Adsorption with purified ICV preparations abolished the neutralizing activity of these antisera against heterologous forms of virus. Hemagglutination-inhibiting antibodies, on the other hand, were produced only after immunization with ECV or its surface proteins. In addition, antibody-dependent cell-mediated cytotoxicity was employed to detect specific antibody response after immunization of rabbits with live virus, ECV, and ICV. Antisera raised against ECV or live virus supported antibody-dependent cell-mediated cytotoxicity, whereas ICV-antiserum failed to do so. The antibody activity present in the former antisera was abolished by absorption with cell membranes from vaccinia-infected cells but not with purified ICV. The data suggest that immunization with inactivated ECV seems to bring about interaction between host immune response (cellular and humoral) and virus-infected cells, which may, perhaps, be necessary for protection against pox virus infection. A similar interaction is unlikely to occur after immunization with inactivated ICV.

Role of Yersinia pseudotuberculosis outer proteins (Yops) in murine humoral immune response

2009 ◽  
Vol 54 (3) ◽  
pp. 239-245 ◽  
Author(s):  
J. M. L. Maia ◽  
L. G. S. Monnazzi ◽  
B. M. M. Medeiros
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Yersinia Pseudotuberculosis ◽  
Humoral Immune

scholarly journals Human Coronaviruses: Counteracting the Damage by Storm

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1457
Author(s):  
Dewald Schoeman ◽  
Burtram C. Fielding
Keyword(s):  
Immune Response ◽  
Severe Disease ◽  
Antiviral Agents ◽  
The Elderly ◽  
Highly Pathogenic ◽  
Vaccine Responses ◽  
Cell Mediated Immune Response ◽  
Inhibition Antibody ◽  
A Cell ◽  
Human Coronaviruses

Over the past 18 years, three highly pathogenic human (h) coronaviruses (CoVs) have caused severe outbreaks, the most recent causative agent, SARS-CoV-2, being the first to cause a pandemic. Although much progress has been made since the COVID-19 pandemic started, much about SARS-CoV-2 and its disease, COVID-19, is still poorly understood. The highly pathogenic hCoVs differ in some respects, but also share some similarities in clinical presentation, the risk factors associated with severe disease, and the characteristic immunopathology associated with the progression to severe disease. This review aims to highlight these overlapping aspects of the highly pathogenic hCoVs—SARS-CoV, MERS-CoV, and SARS-CoV-2—briefly discussing the importance of an appropriately regulated immune response; how the immune response to these highly pathogenic hCoVs might be dysregulated through interferon (IFN) inhibition, antibody-dependent enhancement (ADE), and long non-coding RNA (lncRNA); and how these could link to the ensuing cytokine storm. The treatment approaches to highly pathogenic hCoV infections are discussed and it is suggested that a greater focus be placed on T-cell vaccines that elicit a cell-mediated immune response, using rapamycin as a potential agent to improve vaccine responses in the elderly and obese, and the potential of stapled peptides as antiviral agents.

scholarly journals H-Ras gene takes part to the host immune response to COVID-19

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Salvatore Sciacchitano ◽  
Andrea Sacconi ◽  
Claudia De Vitis ◽  
Giovanni Blandino ◽  
Giulia Piaggio ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Severe Disease ◽  
Host Immune Response ◽  
Severe Form ◽  
Ras Gene ◽  
Peripheral Blood Mononuclear ◽  
Ras Genes

AbstractRas gene family members play a relevant role in cancer, especially when they are mutated. However, they may play additional roles in other conditions beside cancer. We performed gene expression analysis using the NanoString PanCancer IO 360 panel in the peripheral blood mononuclear cell (PBMC) of six COVID-19 patients and we found that H-Ras gene was significantly upregulated, while both K-Ras and N-Ras genes were downregulated. In particular, H-Ras gene upregulation was more evident in COVID-19 patients with a more severe disease. We compared our results with those obtained by analyzing two different and independent datasets, including a total of 53 COVID-19 patients, in which the gene expression analysis was performed using the Immunology_V2 panel. Comparative analysis of the H-Ras gene expression in these patients confirmed our preliminary results. In both of them, in fact, we were able to confirm the upregulation of the expression of the H-Ras gene. The exact role of this specific upregulation of the H-Ras gene in response to SARS-CoV-2 infection and its possible role in cancer still remains to be elucidated. In conclusion, H-Ras gene participates to the host immune response to SARS-CoV-2 virus infection, especially in patients affected by the most severe form of the COVID-19.

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