The Human Viral Challenge (HVC) model has, for many decades, helped in the understanding of respiratory viruses and their role in disease pathogenesis. In a controlled setting using small numbers of volunteers removed from community exposure to other infections, this experimental model enables proof of concept work to be undertaken on novel therapeutics, including vaccines, immunomodulators and antivirals, as well as new diagnostics.Crucially, unlike conventional phase 1 studies, challenge studies include evaluable efficacy endpoints that then guide decisions on how to optimise subsequent field studies, as recommended by the FDA and thus licensing studies that follow. Such a strategy optimises the benefit of the studies and identifies possible threats early on, minimising the risk to subsequent volunteers but also maximising the benefit of scarce resources available to the research group investing in the research. Inspired by the principles of the 3Rs (Replacement, Reduction and Refinement) now commonly applied in the preclinical phase, HVC studies allow refinement and reduction of the subsequent development phase, accelerating progress towards further statistically powered phase 2b studies. The breadth of data generated from challenge studies allows for exploration of a wide range of variables and endpoints that can then be taken through to pivotal phase 3 studies.We describe the disease burden for acute respiratory viral infections for which current conventional development strategies have failed to produce therapeutics that meet clinical need. The Authors describe the HVC model's utility in increasing scientific understanding and in progressing promising therapeutics through development.The contribution of the model to the elucidation of the virus-host interaction, both regarding viral pathogenicity and the body's immunological response is discussed, along with its utility to assist in the development of novel diagnostics.Future applications of the model are also explored.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013893 | PMC |
http://dx.doi.org/10.1186/s12931-018-0784-1 | DOI Listing |
Mol Biol Rep
January 2025
Faculty of Medicine, Department of Gastroenterology, Mersin University, Mersin, Turkey.
Background: Chemokines and their receptors, which regulate lymphoid organ development and immune cell trafficking, are integral to the mechanisms underlying viral control, hepatic inflammation, and liver damage in chronic hepatitis C (CHC) infection. This study explores the potential relationship between serum chemokine levels/polymorphisms and hepatitis C infection in affected individuals, with a particular focus on their utility as biomarkers across different stages of fibrosis.
Methods And Results: Serum levels of the chemokines CXCL11, CXCL12, and CXCL16 were measured in patients with mild/moderate and advanced fibrosis due to CHC, as well as in healthy controls, using the ELISA method.
J Med Virol
January 2025
State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Science, Beijing, China.
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease with a high fatality rate. The clinical diagnosis criteria mainly rely on white blood cell (WBC) and platelet (PLT), which, however, are of limited usage in identifying atypical SFTS. A multicenter study was performed in two hospitals from 2011 to 2023.
View Article and Find Full Text PDFJ Med Virol
January 2025
Laboratório de Morfologia e Morfogênese Viral, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz-Fiocruz, Rio de Janeiro, Brazil.
An unprecedented global outbreak caused by the monkeypox virus (MPXV) prompted the World Health Organization to declare a public health emergency of international concern on July 23, 2022. Therapeutics and vaccines for MPXV are not widely available, necessitating further studies, particularly in drug repurposing area. To this end, the standardization of in vitro infection systems is essential.
View Article and Find Full Text PDFJ Med Virol
January 2025
Department of Morphology and Genetics, Federal University of São Paulo, São Paulo-SP, Brazil.
We identified seven distinct coronaviruses (CoVs) in bats from Brazil, classified into 229E-related (Alpha-CoV), Nobecovirus, Sarbecovirus, and Merbecovirus (Beta-CoV), including one closely related to MERS-like CoV with 82.8% genome coverage. To accomplish this, we screened 423 oral and rectal swabs from 16 different bat species using molecular assays, RNA sequencing, and evolutionary analysis.
View Article and Find Full Text PDFZhongguo Dang Dai Er Ke Za Zhi
January 2025
Department of Neonatology, Children's Hospital of Chongqing Medical University/National Clinical Research Center for Child Health and Disorders/Ministry of Education Key Laboratory of Child Development and Disorders/Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing 400014, China.
Neonates are susceptible to respiratory viral infections, with outbreaks reported in areas with a high population of neonates, such as postpartum care centers and neonatal wards. While specific antiviral drugs are currently available for influenza, symptomatic supportive treatment remains the primary approach for respiratory syncytial virus (RSV), making prevention particularly important. The article closely follows the "Expert recommendations for the prevention of common respiratory viral infections in neonates" and provides an in-depth interpretation of recent breakthroughs in RSV prevention.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!