Investigation of viral and host factors contributing to the pathogenesis of human metapneumovirus infection and development of a subunit vaccine

Le métapneumovirus humain (HMPV) est un virus responsable des infections aiguës des voies respiratoires chez l’enfant ainsi que chez l’adulte. Dans les populations à risque élevée, comme les jeunes enfants, les personnes âgées et les patients immuno-supprimés, le HMPV entraîne une morbidité et une mortalité importante. La pathogenèse de l'infection par le HMPV reste largement inconnue, mais des modèles animaux qui permettent l'étude de cette pathogenèse ont été développés. En effet, le modèle des souris BALB/c a déjà été développé dans le laboratoire du Dr Guy Boivin. Ce modèle murin nous a permis de démontrer que la protéine de fusion (F) contribue à la capacité réplicative du virus, mais qu’elle n’est pas la seule protéine responsable de la virulence de ce virus. De plus, nous avons démontré que le récepteur activé par les protéases (PAR1) contribue de manière significative à la pathogenèse du HMPV. Actuellement, aucun vaccin ou modalité thérapeutique spécifique contre le HMPV sont disponibles. Trois facteurs principaux ont entravé le développement d'un vaccin sûr et efficace contre le HMPV; 1) Le précédent d’une maladie accrue associée à l'utilisation de vaccins inactivées contre la rougeole et le virus respiratoire syncytial (HRSV) et la démonstration d’une maladie accrue suite à une vaccination avec le HMPV inactivé chez les animaux. 2) Le manque de protection à long terme induite par les vaccins contre le HMPV chez les animaux. 3) Notre compréhension limitée des contributions individuelles des protéines virales dans le développement de l'immunité contre le HMPV. En développant un vaccin sous-unitaire comprenant de la protéine F et la protéine de la matrice (M), nous avons démontré que la protéine M contribue de manière significative à la protection chez la souris immunisée.Human metapneumovirus (HMPV) is an important etiological agent of acute respiratory tract infection in both children and adults. In high-risk populations, such as infants, elderly individuals and immunocompromised patients, HMPV causes significant morbidity and mortality. The pathogenesis of HMPV infection remains largely unknown, but animal models of HMPV infection have been developed that allow for the study of such pathogenesis. Indeed, the BALB/c mouse model of HMPV infection was previously developed in Dr Boivin’s laboratory. Using this murine model, we showed that the HMPV fusion (F) protein contributes to, but is not solely responsible for the replicative capacity and virulence of the virus and we demonstrated that the cellular protease-activated receptor-1 (PAR1) significantly contributes to HMPV pathogenesis. To date, no HMPV-specific vaccines or therapeutic modalities are available. Three major factors have haltered the development of a safe and effective HMPV vaccine; 1) the precedent of vaccine-enhanced disease associated with the use of HRSV and measles vaccines and the demonstration of vaccine-enhanced disease upon inactivated HMPV vaccination in animal models. 2) The lack of long-term protection induced by HMPV vaccines in animals. 3) Our limited understanding of the individual contributions of HMPV proteins to host immunity. By developing a subunit vaccine consisting of the HMPV F and matrix (M) protein, we demonstrate that the HMPV M protein significantly contributes to vaccine-induced protection in mice

Comparative evaluation of lumpy skin disease virus-based live attenuated vaccines

Vaccines form the cornerstone of any control, eradication and preventative strategy and this is no different for lumpy skin disease. However, the usefulness of a vaccine is determined by a multiplicity of factors which include stability, efficiency, safety and ease of use, to name a few. Although the vaccination campaign in the Balkans against lumpy skin disease virus (LSDV) was successful and has been implemented with success in the past in other countries, data of vaccine failure have also been reported. It was therefore the purpose of this study to compare five homologous live attenuated LSDV vaccines (LSDV LAV) in a standardized setting. All five LSDV LAVs studied were able to protect against a challenge with virulent LSDV. Aside from small differences in serological responses, important differences were seen in side effects such as a local reaction and a Neethling response upon vaccination between the analyzed vaccines. These observations can have important implications in the applicability in the field for some of these LSDV LAVs

Comparative evaluation of lumpy skin disease virus-based live atenuated vaccines

Vaccines form the cornerstone of any control, eradication and preventative strategy and this is no different for lumpy skin disease. However, the usefulness of a vaccine is determined by a multiplicity of factors which include stability, efficiency, safety and ease of use, to name a few. Although the vaccination campaign in the Balkans against lumpy skin disease virus (LSDV) was successful and has been implemented with success in the past in other countries, data of vaccine failure have also been reported. It was therefore the purpose of this study to compare five homologous live attenuated LSDV vaccines (LSDV LAV) in a standardized setting. All five LSDV LAVs studied were able to protect against a challenge with virulent LSDV. Aside from small differences in serological responses, important differences were seen in side effects such as a local reaction and a Neethling response upon vaccination between the analyzed vaccines. These observations can have important implications in the applicability in the field for some of these LSDV LAVs.The Bill & Melinda Gates Foundation, the GALVmed project Nr CAO-R34A0856 on lumpy skin disease and the Belgian Federal Public Service of Health, Food Chain Safety and Environment through the contract RT 15/3 (LUMPY SKIN 1).http://www.mdpi.com/journal/vaccinespm2022Veterinary Tropical Disease

Long-term impairment of Streptococcus pneumoniae lung clearance is observed after initial infection with influenza A virus but not human metapneumovirus in mice.

Human metapneumovirus (hMPV) is a paramyxovirus responsible for respiratory tract infections in humans. Our objective was to investigate whether hMPV could predispose to long-term bacterial susceptibility, such as previously observed with influenza viruses. BALB/c mice were infected with hMPV or influenza A and, 14 days following viral infection, challenged with Streptococcus pneumoniae. Only mice previously infected with influenza A demonstrated an 8% weight loss of their body weight 72 h following S. pneumoniae infection, which correlated with an enhanced lung bacterial replication of >7 log(10) compared with pneumococcus infection alone. This enhanced bacterial replication was not related to altered macrophage or neutrophil recruitment or deficient production of critical cytokines. However, bacterial challenge induced the production of gamma interferon in bronchoalveolar lavages of influenza-infected mice, but not in those of hMPV-infected animals. In conclusion, hMPV does not cause long-term impairment of pneumococcus lung clearance, in contrast to influenza A virus.info:eu-repo/semantics/publishe

A role for serotonin signaling in cross-modal plasticity modulation

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Serotonergic modulation of visual cortex plasticity

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Understanding the role of disease knowledge and risk perception in shaping preventive behavior for selected vector-borne diseases in Guyana

Background: Individual behavior, particularly choices about prevention, plays a key role in infection transmission of vector-borne diseases (VBDs). Since the actual risk of infection is often uncertain, individual behavior is influenced by the perceived risk. A low risk perception is likely to diminish the use of preventive measures (behavior). If risk perception is a good indicator of the actual risk, then it has important implications in a context of disease elimination. However, more research is needed to improve our understanding of the role of human behavior in disease transmission. The objective of this study is to explore whether preventive behavior is responsive to risk perception, taking into account the links with disease knowledge and controlling for individuals’ socioeconomic and demographic characteristics. More specifically, the study focuses on malaria, dengue fever, Zika and cutaneous leishmaniasis (CL), using primary data collected in Guyana–a key country for the control and/or elimination of VBDs, given its geographic location. Methods and findings: The data were collected between August and December 2017 in four regions of the country. Questions on disease knowledge, risk perception and self-reported use of preventive measures were asked to each participant for the four diseases. A structural equation model was estimated. It focused on data collected from private households only in order to control for individuals’ socioeconomic and demographic characteristics, which led to a sample size of 497 participants. The findings showed evidence of a bidirectional association between risk perception and behavior. A one-unit increase in risk perception translated into a 0.53 unit increase in self-reported preventive behavior for all diseases, while a one-unit increase in self-reported preventive behavior (i.e. the use of an additional measure) led to a 0.46 unit decrease in risk perception for all diseases (except CL). This study also showed that higher education significantly improves knowledge and that better knowledge increases the take up of preventive measures for malaria and dengue, without affecting risk perception. Conclusions: In trying to reach elimination, it appears crucial to promote awareness of the risks and facilitate access to preventive measures, so that lower risk perception does not translate into lower preventive behavior

No correlation between time-linked plasma and CSF Abeta levels.

Plasma beta-amyloid protein (Abeta) isoforms are considered potential biomarkers for Alzheimer's disease (AD) and dementia. The relation between plasma and cerebrospinal fluid (CSF) levels of Abeta isoforms remains unclear. In order to identify possible correlations between Abeta levels in plasma and CSF we determined Abeta levels in time-linked plasma and CSF samples. Abeta concentrations in plasma (Abeta(1-42) and Abeta(N-42)) and CSF (Abeta(1-42)) samples from 49 AD patients, 47 non-Alzheimer's disease dementia (NONAD) patients, 39 MCI patients and 29 controls were determined using a multi-parameter fluorimetric bead-based immunoassay using xMAP((R)) technology (for plasma) and a conventional single-parameter ELISA (for CSF). Plasma Abeta(1-42) concentrations did not correlate with CSF Abeta(1-42) concentrations in the total study population, or in the different diagnostic groups. No correlations between plasma Abeta(N-42) and CSF Abeta(1-42) levels were found either. The CSF/serum albumin index did not show any significant differences between AD, NONAD, MCI and controls. These results suggest that the Abeta levels in plasma are independent of the Abeta levels in CSF both in dementia and controls. The fact that CSF and plasma Abeta do not correlate in patients as well as controls and no significant differences in plasma Abeta(1-42) or Abeta(N-42) between patients and controls can be detected hampers the diagnostic utility of the plasma Abeta levels as biomarkers for dementia.info:eu-repo/semantics/publishe