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Publications (67)
Frailty describes an age-associated state in individuals with an increased vulnerability and less resilience against adverse outcomes. To score frailty, studies have employed the questionnaires, such as the SF-36 and EQ-5D-3L, or the Frailty Index, a composite score based on deficit accumulation. Furthermore, ageing of the immune system is often ac...
Respiratory syncytial virus (RSV) infections are a major cause of bronchiolitis and pneumonia in infants and older adults, for which there is no known correlate of protection. Increasing evidence suggests that Fc-mediated antibody effector functions have an important role, but little is known about the development, heterogeneity, and durability of...
Effective vaccine-induced immune responses are particularly essential in older adults who face an increased risk of immunosenescence. However, the complexity and variability of the human immune system make predicting vaccine responsiveness challenging. To address this knowledge gap, our study aimed to characterize immune profiles that are predictiv...
The generation of a specific long-term immune response to SARS-CoV-2 is considered important for protection against COVID-19 infection and disease. Memory B cells, responsible for the generation of antibody-producing plasmablasts upon a new antigen encounter, play an important role in this process. Therefore, the induction of memory B cell response...
Background:
Patients with haematological malignancies have impaired antibody responses to SARS-CoV-2 vaccination. We aimed to investigate whether a fourth mRNA COVID-19 vaccination improved antibody quantity and quality.
Methods:
In this cohort study, conducted at 5 sites in the Netherlands, we compared antibody concentrations 28 days after 4 mR...
Introduction
Respiratory infections are a common cause of illness in older adults, potentially resulting in severe morbidity or mortality. While up to 10% of respiratory infections in this population are caused by one of the four human coronaviruses (hCoVs), OC43, HKU1, NL63, and 229E, data on hCoV epidemiological and immunological responses are li...
Vaccines are currently the best available interventions to protect individuals from infectious diseases. However, immunosenescence, described as immune dysfunction at older age, leads to lower responsiveness to vaccines. We analyzed a broad set of immune cell subsets (n=129) in whole-blood of 308 individuals (aged 25–98) pre- and post-flu vaccinati...
Immunosenescence describes immune dysfunction observed in older individuals. To identify individuals at‐risk for immune dysfunction, it is crucial to understand the diverse immune phenotypes and their intrinsic functional capabilities. We investigated immune cell subsets and variation in the aging population. We observed that inter‐individual immun...
Aging leads to alterations in the immune system that result in ineffective responsiveness against pathogens. Features of this process, collectively known as immunosenescence, accumulate in CD8+ T cells with age and have been ascribed to differentiation of these cells during the course of life. Here we aimed to identify novel markers in CD8+ T cells...
Influenza-like illness (ILI) can be caused by a range of respiratory viruses. The present study investigates the contribution of influenza and other respiratory viruses, the occurrence of viral co-infections, and the persistence of the viruses after ILI onset in older adults. During the influenza season 2014–2015, 2366 generally healthy community-d...
[This corrects the article DOI: 10.3389/fimmu.2022.817876.].
Background
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to considerable morbidity/mortality worldwide, but most infections, especially among children, have a mild course. However, it remains largely unknown whether infected children develop cellular immune memory.
Methods
To determine whether a memory T cell response is bei...
Influenza-like illness (ILI), a disease caused by respiratory pathogens including influenza virus, is a major health concern in older adults. There is little information on changes and recovery dynamics of the nasopharyngeal (NP) microbiota of older adults associated with an ILI. Here, we compared the NP microbiota in older adults reporting (n = 24...
Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to considerable morbidity/mortality worldwide, but most infections, especially among children, have a mild course. However, it remains largely unknown whether infected children develop cellular immune memory.
Methods: To determine whether a memory T cell response is be...
Background
Older adults are more susceptible to respiratory pathogens, several of which have been associated with an altered respiratory microbiota. Influenza-like illness (ILI), a disease caused by respiratory pathogens including but not exclusively by influenza virus, is a major health concern in this population. However, there is little informat...
Severe respiratory viral infectious diseases such as influenza and COVID-19 especially affect the older population. This is partly ascribed to diminished CD8⁺ T-cell responses a result of aging. The phenotypical diversity of the CD8⁺ T-cell population has made it difficult to identify the impact of aging on CD8⁺ T-cell subsets associated with dimin...
Latent infection with cytomegalovirus (CMV) is assumed to contribute to the age-associated decline of the immune system. CMV induces large changes in the T-cell pool and may thereby affect other immune responses. CMV is expected to impact especially older adults, who are already at higher risk of severe disease and hospitalization upon infections s...
CD8 ⁺ T cells play an important role in protection against viral infections. With age, changes in the T-cell pool occur, leading to diminished responses against both new and recurring infections in older adults. This is thought to be due to a decrease in both T-cell numbers and T-cell receptor (TCR) diversity. Latent infection with cytomegalovirus...
Background
People aged 60 years or older are at high risk for respiratory infections, one of the leading causes of mortality worldwide. Vaccination is the main way to protect against these infections; however, vaccination is less effective in older adults than in younger adults due to ageing of the immune system, so innovative strategies that impro...
Background: In older adults pneumococcal disease is strongly associated with respiratory viral infections, but the impact of viruses on Streptococcus pneumoniae carriage prevalence and load remains poorly understood. Here, we investigated the effects of influenza-like illness (ILI) on pneumococcal carriage in community-dwelling older adults.
Method...
Respiratory syncytial virus (RSV) can cause severe morbidity and mortality in certain risk groups, especially infants and older adults. Currently no (prophylactic) treatment is available, except for a partially effective yet highly expensive monoclonal antibody. RSV therefore remains a major public health concern. To allow targeted development of n...
Serology is a crucial part of the public health response to the ongoing SARS-CoV-2 pandemic, but there are still many unknowns. Here, we describe the development, validation and clinical evaluation of a protein micro-array as a quantitative multiplex immunoassay that can identify S and N-directed SARS-CoV-2 IgG antibodies with high specificity and...
Background:
The COVID-19 pandemic necessitates a better understanding of the kinetics of antibody production induced by infection with SARS-CoV-2. We aimed to develop a high throughput multiplex assay to detect antibodies to SARS-CoV-2 to assess immunity to the virus in the general population.
Methods:
Spike protein subunits S1 and RBD, and Nucl...
Background
The COVID-19 pandemic demands detailed understanding of the kinetics of antibody production induced by infection with SARS-CoV-2. We aimed to develop a high throughput multiplex assay to detect antibodies to SARS-CoV-2 to assess immunity to the virus in the general population.
Methods
Spike protein subunits S1 and RBD, and Nucleoprotein...
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
H7 avian influenza viruses represent a major public health concern, and worldwide outbreaks raise the risk of a potential pandemic. Understanding the memory B cell response to avian (H7) influenza virus infection in humans could provide insights in the potential key to human infection risks. We investigated an epizootic of the highly pathogenic A(H...
While currently used influenza vaccines are designed to induce neutralizing antibodies, little is known on T cell responses induced by these vaccines. The 2009 pandemic provided us with the opportunity to evaluate the immune response to vaccination in a unique setting. We evaluated both antibody and T cell responses in a cohort of public health car...
Influenza peptide antigens coding for conserved T cell epitopes have the capacity to induce cross-protective influenza-specific immunity. Short peptide antigens used as a vaccine, however, often show poor immunogenicity. In this study, we demonstrate that whole-inactivated influenza virus (WIV) acts as an adjuvant for influenza peptide antigens, as...
Older adults are more vulnerable to influenza virus infection and at higher risk for severe complications and influenza-related death compared to younger adults. Unfortunately, influenza vaccine responses tend to be impaired in older adults due to aging of the immune system (immunosenescence). Latent infection with cytomegalovirus (CMV) is assumed...
Background:
Data on the relative contribution of influenza virus and other respiratory pathogens to respiratory infections in community-dwelling older adults (≥60 years) are needed.
Methods:
A prospective observational cohort study was performed in the Netherlands during 2 winters. Nasopharyngeal and oropharyngeal swabs were collected during inf...
HLA-A*0201 binding of CPLs of influenza epitopes; GILGFVFTL (M158-66), FMYSDFHFI (PA46-54) and (C) NMLSTVLGV (PB1413-421).
(XLSX)
GILG, FMY and NML specific CD8+ T cell responses after stimulation with CPLs in in vitro and ex vivo screening models.
(XLSX)
Flow cytometry dot plots showing IFN-γ-positive CD4+ T cells of HLA-A2+ transgenic mice.
(DOCX)
Epitope MHC specificity control experiment in C57BL/6 mice.
(DOCX)
Heat map representation of Table 3.
FP binding scores HLA-A*0301 peptides.
(XLSX)
Heat map representation of Table 1.
FP binding scores of selected HLA-A*0201 peptides.
(XLSX)
Incidence of pneumococcal disease is disproportionally high in infants and elderly. Naso-pharyngeal colonisation by Streptococcus pneumoniae is considered a prerequisite for disease but unlike in children, carriage in elderly is rarely detected. Here, we tested for S. pneumoniae in nasopharyngeal and saliva samples collected from community-dwelling...
An effective immune response against viral infections depends on the activation of cytotoxic T cells that can clear infection by killing virus-infected cells. Proper activation of these T cells depends on professional antigen-presenting cells, such as dendritic cells (DCs). In this review, we will discuss the potential of peptide-based vaccines for...
Seasonal influenza causes more morbidity and mortality in older adults than in young adults, apparently because of a decline in immune function with increasing age, known as immunosenescence. In this study, we compared the capacity of dendritic cells (DCs) from healthy older adults (≥65 years) with DCs from healthy young adults (20-40 years) to ini...
WHO 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. Thi...
Chronic infection results in continuous formation and exhaustion of effector CD8 T cells and in failure of memory CD8 T cell development. Expression of CD70 and other molecules that provide costimulation to T cells is maintained during chronic infection. To analyze the impact of constitutive CD70-driven costimulation, we generated transgenic mice e...
Recently, we showed that Epstein-Barr virus (EBV)-positive gastric carcinoma (GC) forms a distinct clinicopathologic entity with a better prognosis due to lower incidence of lymph node metastases (LN+). Here we investigated whether in EBV-positive GC more pronounced activation of cellular immune responses is associated with absence of (micro)metast...
To determine at what stage during gastric carcinogenesis Epstein-Barr virus (EBV) enters the gastric epithelial cells, the presence of EBV was investigated in two pathogenetically related but distinct forms of adenocarcinoma of the stomach-gastric carcinoma of the intact stomach (GCIS) and gastric stump carcinoma (GSC)-and their presumed precursor...
Epstein-Barr virus (EBV) is detected in a substantial subgroup of gastric adenocarcinomas worldwide. We have previously reported that these EBV-positive gastric carcinomas carry distinct genomic aberrations. In the present study, we analyzed a large cohort of EBV-positive and EBV-negative gastric adenocarcinomas for their clinicopathologic features...
The in vivo expression of the Epstein-Barr virus (EBV) BamHI-A rightward transcripts (BARTs) as well as the putative BART-encoded BARF0 and RK-BARF0 proteins in various EBV-associated malignancies was investigated. RT-PCRs specific for the different splice variants of the BARTs and both a nucleic acid sequence-based amplification assay and an RT-PC...
Epstein-Barr virus (EBV) has been suggested to play a role in hepatocellular carcinoma (HCC). However, reports on detailed EBV transcript analyses in HCCs are limited. It was shown recently that expression of the transforming BARF1 (BamHI A rightward open reading frame 1) gene of EBV is restricted to latently EBV-infected epithelial malignancies, i...
Epstein-Barr virus (EBV) is associated with a substantial number of gastric adenocarcinomas worldwide, as confirmed by EBER1/2-RNA in situ hybridization (RISH). In the present study, we developed a rapid and sensitive PCR-based prescreening method for the detection of EBV in gastric carcinomas to reduce the amount of laborious EBER1/2-RISH assays t...
A quantitative polymerase chain reaction-enzyme immunoassay (Q-PCR-EIA) was developed to measure the amount of human papillomavirus (HPV) 16 DNA per genome equivalent in cervical scrapings. The quantitative approach was based on a combined competitive PCR for both HPV 16, using the general primer GP5+/6+ PCR, and beta-globin DNA. The two competitiv...
