The Challenge
Seasonal influenza (“flu”) causes significant morbidity and mortality each year and a pandemic influenza continues to pose a worldwide threat. Government health agencies and organisations and a large number of academic, public and private organisations, encourage development of universal / broad spectrum flu vaccines. Novel correlates of protection are being explored and the role of cellular
immunity has come to the forefront of vaccine research. Healthy volunteer human challenge models of wild-type influenza will play a major role in this development process.
Proven flu disease models
hVIVO has been studying influenza for over 20 years and been conducting influenza human challenge studies with our flu disease models for more than 15 years.
As the industry leader in conducting human viral challenge studies, hVIVO have developed a large Virobase, of clinical data paired with virological data, host genetics and immunology combined with an extensive biorepository of blood and respiratory samples. This “Virometrics” resource, in conjunction with our unique insight into the host response to viral disease, allows hVIVO to tailor study designs to each IMP.
Flu Vaccines
Conceptual Challenges
Demonstrating efficacy of novel vaccines in the field is time-consuming, costly and associated with risk
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Initial exposure to virus unknown
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Variation in circulating strains
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Large study size and duration
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Difficult to power for clinical efficacy
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Seasonality limitations
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Biomarker identification difficult
Flu Vaccines
hVIVO Human Challenge Models: Towards a deeper understanding
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Effective exploration of vaccine efficacy & correlates of protection
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Match study design to product mechanism of action
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Immunological Assays
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Host Response Analysis
Primary Endpoints:
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Reduction in incidence of symptomatic infection
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Reduction in disease severity
Antivirals/Treatments
Conceptual Challenges
Establishing efficacy of anitvirals in early clinical trials in influenza is challenging
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Initial exposure to virus unknown
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Dose ranging and timing difficult
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Comorbitities and other confounders
Flu Vaccines
hVIVO Human Challenge Models: Towards a deeper understanding
Clinical proof-of concept and dosing finding delivered in a controlled setting
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Study design matched to investigational product mechanism of actions
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Optimisation of treatment timing
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Time-dependent measurements of biomarkers
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Triggered-dosing options (time or virological)
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Controlled strain exposure
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Consistent placebo response
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Flu season independent
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Efficient resistance monitoring
Immunomodulators
Conceptual Challenges
Demonstrating clinical efficacy in early stage field trials is challenging
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Baseline prior to infection unachievable, difficult to establish host response
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Effect with/without standard of care treatment difficult to establish
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Large study size and duration
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Seasonality limitations
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Circulating strain variation
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Biomarker identification difficult
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Initial exposure to virus unknown
Flu Vaccines
hVIVO Human Challenge Models: Towards a deeper understanding
Clinical proof-of concept and dosing finding delivered in a controlled setting
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Well controlled quarantine environments
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Baseline well established prior to infection
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Appropriate for both prophylaxis and treatment
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Flexible dosing and timing
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Establish safety & efficacy to impact infected subjects host response
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Investigate and demonstrate target engagement
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Controlled combination-treatment with drug and standard of care or antivirals
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