Wie de schoen past …:Op weg naar vaccinaties op maat

In haar inaugurele lezing 'Wie de schoen past 2.0....' zal Professor Debbie van Baarle ingaan op het belang van het verbeteren van vaccinatiestrategieën voor ouderen en kwetsbare patiënten, met name door gebruik te maken van nieuwe gepersonaliseerde strategieën.Vaccinatie is een zeer effectief middel om levensbedreigende infectieziekten te voorkomen, met name in de groeiende populatie ouderen. Met het ouder worden neemt de capaciteit van het immuunsysteem, dat verantwoordelijk is voor de bescherming tegen infecties, af. Dit leidt tot een verhoogd infectierisico met een ernstiger ziekteverloop, maar ook tot een lagere effectiviteit van vaccinatie.Van Baarle's onderzoek richt zich op het begrijpen van de immuunmechanismen die betrokken zijn bij bescherming, specifiek de T-celrespons. Een beter begrip van hoe deze T-cellen virussen herkennen, de functies die belangrijk zijn bij het bestrijden ervan en de levensduur van deze respons zal inzicht geven in belangrijke immuunreacties die nodig zijn voor effectieve vaccinatie.Standaard vaccinatieprogramma's zijn succesvol geweest in het beschermen van de bevolking tegen infectieziekten. Echter, met een toenemend aantal ouderen is een beter passende strategie nodig om diegenen te beschermen die dat het meest nodig hebben. Daarom willen we voorspellers van een vaccinatierespons vinden, zodat we daarmee ouderen kunnen identificeren die alternatieve vaccinatiestrategieën nodig hebben.De resultaten van onze studies zullen gebruikt worden om individuen te identificeren die risico lopen op (bepaalde) infectieziekten en om vaccinatiestrategieën te sturen om de immuunrespons op virussen te verbeteren en daardoor vaccinaties te verbeteren.Als resultaat zal de focus op specifieke risico/kwetsbare groepen van een "one size fits all" aanpak verschuiven naar een nieuw tijdperk van gepersonaliseerde vaccinatie

HCV monoinfection and HIV/HCV coinfection enhance T-cell immune senescence in injecting drug users early during infection

Background: Injecting drug users (IDU) are at premature risk of developing multimorbidity and mortality from causes commonly observed in the elderly. Ageing of the immune system (immune-senescence) can lead to premature morbidity and mortality and can be accelerated by chronic viral infections. Here we investigated the impact of HCV monoinfection and HIV/HCV coinfection on immune parameters in (ex-) IDU. We analyzed telomere length and expression of activation, differentiation and exhaustion markers on T cells at baseline (t = 1) and at follow-up (t = 2) (median interval 16.9 years) in IDU who were: HCV mono-infected (n = 21); HIV/HCV coinfected (n = 23) or multiple exposed but uninfected (MEU) (n = 8). Results: The median time interval between t = 1 and t = 2 was 16.9 years. Telomere length within CD4(+) and CD8(+) T cells decreased significantly over time in all IDU groups (p <= 0.012). CD4(+) T-cell telomere length in HCV mono-infected IDU was significantly reduced compared to healthy donors at t = 1 (p <0.008). HIV/HCV coinfected IDU had reduced CD4(+) and CD8(+) T-cell telomere lengths (p <= 0.002) to healthy donors i at t = 1. This was related to persistent levels of immune activation but not due to increased differentiation of T cells over time. Telomere length decrease was observed within all T-cell subsets, but mainly found in immature T cells (CD27(+)CD57(+)) (p <= 0.015). Conclusions: HCV mono-infection and HIV/HCV coinfection enhance T-cell immune-senescence. Our data suggest that this occurred early during infection, which warrants early treatment for both HCV and HIV to reduce immune senescence in later lif

Socioeconomic Status Is Associated With Antibody Levels Against Vaccine Preventable Diseases in the Netherlands.

Background: We investigated whether low socioeconomic status (SES), which is associated with reduced health and life expectancy, might play a role in increased risk for infectious diseases. Therefore, we explored the association between SES and immunoglobulin G (IgG) levels against various pathogens. Methods: We analyzed the association between SES [educational level and net household income (NHI)] and serum IgG concentration against measles, mumps, rubella, varicella, Haemophilus influenzae type B (HiB), pneumococcus, meningococcus serogroup C (MenC), and cytomegalovirus (CMV) collected within a national cross-sectional serosurvey (2006/2007) using linear regression analyses among non-vaccinated individuals. Results: Higher educational level was associated with higher IgG concentrations against measles (GMC ratio 1.34, 95% CI 1.18-1.53) and rubella (1.13, 1.02-1.25) compared to low education level. In contrast, higher education level was associated with lower IgG concentrations against pneumococcus (0.78, 0.70-0.88), MenC (0.54, 0.44-0.68), and CMV (0.23, 0.18-0.31) compared to low education level. This pattern was also evident when NHI was used as SES indicator. Conclusion: Our study suggests that socioeconomic status is associated with antibody levels in a pathogen-dependent manner. The results suggest that differences in serological response upon infection or differences in exposure might be involved in the variation in IgG levels between SES groups

Biological Characteristics of HLA-G and Its Role in Solid Organ Transplantation

Organ transplantation is a lifesaving option for patients with advanced diseases. Rejection is regarded as one of the most severe risk factors post-transplantation. A molecule that contributes to immune tolerance and resisting rejection is human leukocyte antigen (HLA)-G, which belongs to the non-classical major histocompatibility complex class (MHC) I family. HLA-G was originally found to play a role during pregnancy to maintain immune tolerance between mother and child. It is expressed in the placenta and detected in several body fluids as soluble factor as well as different membrane isoforms on cells. Recent findings on HLA-G show that it can also play multifaceted roles during transplantation. This review will explain the general characteristics and biological function of HLA-G and summarize the views supporting the tolerogenic and other roles of HLA-G to better understand its role in solid organ transplantation (SOT) and its complications. Finally, we will discuss potential future research on the role of HLA-G in prevention, diagnosis, and treatment in SOT

Effect of DMARDs on the immunogenicity of vaccines

Vaccines are important for protecting individuals at increased risk of severe infections, including patients undergoing DMARD therapy. However, DMARD therapy can also compromise the immune system, leading to impaired responses to vaccination. This Review focuses on the impact of DMARDs on influenza and SARS-CoV-2 vaccinations, as such vaccines have been investigated most thoroughly. Various data suggest that B cell depletion therapy, mycophenolate mofetil, cyclophosphamide, azathioprine and abatacept substantially reduce the immunogenicity of these vaccines. However, the effects of glucocorticoids, methotrexate, TNF inhibitors and JAK inhibitors on vaccine responses remain unclear and could depend on the dosage and type of vaccination. Vaccination is aimed at initiating robust humoral and cellular vaccine responses, which requires efficient interactions between antigen-presenting cells, T cells and B cells. DMARDs impair these cells in different ways and to different degrees, such as the prevention of antigen-presenting cell maturation, alteration of T cell differentiation and selective inhibition of B cell subsets, thus inhibiting processes that are necessary for an effective vaccine response. Innovative modified vaccination strategies are needed to improve vaccination responses in patients undergoing DMARD therapy and to protect these patients from the severe outcomes of infectious diseases.</p

Effect of DMARDs on the immunogenicity of vaccines

Vaccines are important for protecting individuals at increased risk of severe infections, including patients undergoing DMARD therapy. However, DMARD therapy can also compromise the immune system, leading to impaired responses to vaccination. This Review focuses on the impact of DMARDs on influenza and SARS-CoV-2 vaccinations, as such vaccines have been investigated most thoroughly. Various data suggest that B cell depletion therapy, mycophenolate mofetil, cyclophosphamide, azathioprine and abatacept substantially reduce the immunogenicity of these vaccines. However, the effects of glucocorticoids, methotrexate, TNF inhibitors and JAK inhibitors on vaccine responses remain unclear and could depend on the dosage and type of vaccination. Vaccination is aimed at initiating robust humoral and cellular vaccine responses, which requires efficient interactions between antigen-presenting cells, T cells and B cells. DMARDs impair these cells in different ways and to different degrees, such as the prevention of antigen-presenting cell maturation, alteration of T cell differentiation and selective inhibition of B cell subsets, thus inhibiting processes that are necessary for an effective vaccine response. Innovative modified vaccination strategies are needed to improve vaccination responses in patients undergoing DMARD therapy and to protect these patients from the severe outcomes of infectious diseases.</p