Viral load appears to drive disease manifestations in humans with RSV infection. The observed parallel viral and disease kinetics support a potential clinical benefit of RSV antivirals. This reproducible model facilitates the development of future RSV therapeutics.

A small armentarium of anti-influenza drugs now exists, and includes the M2 blockers (amantadine and rimantadine) and the neuraminidase inhibitors (Relenza and Tamiflu). The neuraminidase inhibitors have certain advantages, including a broader spectrum of antiviral activity, including influenza A and B viruses. On the other hand, there is now much clinical experience with the M2 blockers, and these drugs are inexpensive. It is clear that influenza in different community groups needs to be managed in specific and targeted ways. For example, in the over-65-years and at-risk groups, vaccination will remain a mainstay of disease prevention. However, up to 40% of those in these groups may fail to receive vaccine, and therefore the antivirals can be used therapeutically, or, in defined circumstances, as prophylactics. At present, influenza is hardly managed in the community. The infrequent global outbreaks, pandemics, present further problems. The more extensive use of the two classes of antivirals, and also vaccines, in the important interpandemic years will provide a very significant investment in health benefits in the face of a new pandemic virus in an otherwise completely vulnerable population.

Background  Influenza A viruses are of major concern for public health, causing worldwide epidemics associated with high morbidity and mortality. Vaccines are critical for protection against influenza, but given the recent emergence of new strains with pandemic potential, and some limitations of the current production systems, there is a need for new approaches for vaccine development. Objective  To demonstrate the immunogenicity and protective efficacy of plant‐produced influenza antigens. Method  We engineered, using influenza A/Wyoming/3/03 (H3N2) as a model virus, the stem and globular domains of hemagglutinin (HA) produced in plants as fusions to a carrier protein and used purified antigens with and without adjuvant for ferret immunization. Results  These plant‐produced antigens were highly immunogenic and conferred complete protection against infection in the ferret challenge model. The addition of plant‐produced neuraminidase was shown to enhance the immune response in ferrets. Conclusions  Plants can be used as a production vehicle for vaccine development against influenza. Domains of HA can generate protective immune responses in ferrets.

Viral and disease dynamics in experimental human infections suggest that reducing RSV load, if timed similarly to clinically-effective influenza antivirals, might be expected to have a similar or greater window of opportunity for reducing clinical RSV disease.

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.Electronic supplementary materialThe online version of this article (10.1186/s12931-018-0784-1) contains supplementary material, which is available to authorized users.