RSV vaccines & treatments

The Challenge

Respiratory syncytial virus (RSV) is the single most important cause of lower respiratory tract infection (LRTI) in infants and young children worldwide and can cause LRTI in elderly and immunocompromised patients; it is associated with significant morbidity and mortality in these populations. However, RSV is recognised as a significant cause of respiratory illness in all age groups and there are no effective licensed therapies generally available. Novel correlates of protection are being explored and developing vaccine correlates can assist to bridging other populations. Healthy volunteer human challenge models will play a major role in the development process.

Validated RSV Models

RSV challenge model now validated across multiple studies

New Older Adults Model available

Conducted a number of human RSV challenge studies for a range of customers:
• Currently, the only validated RSV challenge model commercially available
• Validated across multiple studies with vaccines and antivirals directed towards RSV
• New RSV challenge model available in Older Adults (60-75) – targets population
associated with significant unmet need in RSV

Vaccines

Conceptual Challenges

  • Testing proof of concept in the target population (pediatrics or elderly)

  • No clear product development pathway

  • Correlates of infection are poorly understood

  • Lack of fully translatable immunogenicity animal models

Flu Vaccines

hVIVO Human Challenge Models: Towards a deeper understanding

  • Healthy adult model enables fast efficient proof of concept demonstration and safety in disease model before moving to at risk populations in field trials

  • Elderly (60+) model, enables demonstration of proof of concept in target population with weakened immunity

  • For vaccines, both options facilitate efficient investigation of known and novel correlates of vaccine protective effect

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Antivirals/Treatments

Conceptual Challenges

  • Testing proof of concept in the target population (pediatrics or elderly)

  • Correlates of infection are poorly understood

  • Lack of fully translatable immunogenicity animal models

Flu Vaccines

hVIVO Human Challenge Models: Towards a deeper understanding

Study design matched to investigational product mechanism of actions

  • Optimisation of treatment timing

  • Time-dependent measurements of biomarkers

  • Triggered-dosing options (time or virological)

  • Controlled strain exposure

  • Consistent placebo response

  • Efficient resistance monitoring

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Immunomodulators

Conceptual Challenges

  • Limited RSV immunomodulators in development

  • Limited focus on adult/elderly populations

Flu Vaccines

hVIVO Human Challenge Models: Towards a deeper understanding

  • Well controlled quarantine environments

  • Baseline well established prior to infection

  • Appropriate for both prophylaxis and treatment

  • Flexible dosing and timing

  • Establish safety & efficacy to impact infected subjects host response

  • Investigate and demonstrate target engagement

  • Controlled combination-treatment with drug and standard of care or antivirals

Click for the full RSV Fact Sheet

RSV Scientific Papers

Scientific Paper 106 – Effect of pre-existing serum and mucosal antibody on experimental respiratory syncytial virus (RSV) challenge and infection of adults

Scientific Paper 97: Comparing influenza and RSV viral and disease dynamics in experimentally infected adults predicts clinical effectiveness of RSV antivirals.

Scientific Paper 89 : A randomized, double-blind, placebo-controlled study of an RNAi-based therapy directed against respiratory syncytial virus.

Scientific Paper 107 : Activity of Oral ALS-008176 in a Respiratory Syncytial Virus Challenge Study

Scientific Paper 72 : A throat lozenge containing amyl meta cresol and dichlorobenzyl alcohol has a direct virucidal effect on respiratory syncytial virus, influenza A and SARS-CoV.

Scientific Paper 65 : Strong local and systemic protective immunity induced in the ferret model by an intranasal virosome-formulated influenza subunit vaccine.

Scientific Paper 23 : Neutralization escape mutants of type A influenza virus are readily selected by antisera from mice immunized with whole virus: a possible mechanism for antigenic drift.

Scientific Paper 34 : Longitudinal study of an epitope-biased serum haemagglutination-inhibition antibody response in rabbits immunized with type A influenza virions.

Scientific Paper 57 : The H274Y mutation in the influenza A/H1N1 neuraminidase active site following oseltamivir phosphate treatment leave virus severely compromised both in vitro and in vivo.

Scientific Paper 88 : Gene expression signatures diagnose influenza and other symptomatic respiratory viral infections in humans.