The current state of H5N1 vaccines and the use of the ferret model for influenza therapeutic and prophylactic development

Abstract

Highly pathogenic avian influenza H5N1 is a threat to global public health as a natural pandemic causing agent but has recently been considered a bioterrorism concern. The evolving view of the H5N1 virus necessitates the re-evaluation of the current status of H5N1 therapeutics and prophylactics, in particular the preparation of viable H5N1 vaccination strategies as well as the use of ferrets in influenza research. Here the highly pathogenic H5N1 virus dilemma is discussed in context with the current H5N1 vaccine status and the use of the ferret model. Previously, the development of various H5N1 vaccine platforms have been attempted, many of them tested in the ferret model, including vector vaccines, adjuvant vaccines, DNA vaccines, and reverse engineered vaccines. Moreover, as ferrets are a superlative animal model for influenza investigation and vaccine testing, it is imperative that this model is recognized for its uses in prophylactic development and not only as an agent for creating transmissible influenza viruses. Elucidating the ferret immune response and creating ferret immune reagents remain important goals in conjunction with the development and manufacture of H5N1 vaccines. In summary, an efficacious H5N1 vaccine is urgently needed and the ferret model remains an appropriate model for its development.J Infect Dev Ctries 2012; 6(6):465-469.

Impaired heterologous immunity in aged ferrets during sequential influenza A H1N1 infection

“…Ferrets closely mimic the clinical manifestations of influenza infection in humans as shown previously (Banner and Kelvin, 2012; Belser et al, 2011; Huang et al, 2011; Huang et al, 2013; Rowe et al, 2010). Naïve adult (4-6 months old) and aged (≥ 4 years old) male ferrets were placed into groups for either homologous or heterologous H1N1 sequential infection studies.…”

Influenza Vaccination Accelerates Recovery of Ferrets from Lymphopenia

“…Ferrets are considered the most appropriate model animal for the study of human influenza disease and immunity, because they can be infected directly with human virus isolates and generally show similar clinical signs and disease severity to humans infected with the similar viruses [15]–[18]. Ferrets are large enough that serial blood samples of ∼250 µl, sufficient to perform flow cytometric analysis, can be taken daily without depleting blood volume or cellularity.…”

“…The ferret remains the most widely accepted small animal model for influenza virus infection and vaccine protection studies [15]–[18]. Ferrets are readily infected with human and avian influenza viruses without the need for prior adaptation, and in general the course of infection in ferrets recapitulates that seen in susceptible humans.…”

Pathogenic influenza B virus in the ferret model establishes lower respiratory tract infection

“…Ferrets are a suitable model to study influenza infection as they manifest human-like flu symptoms and immune responses (Banner & Kelvin, 2012; Hamelin et al , 2010; Hause et al , 2013; Huang et al , 2013; León et al , 2013). Previously, we found distinct clinical and immunological patterns between ferrets infected with B/Vic and B/Yam lineages, where B/Vic appeared to be the more virulent lineage (Huang et al , 2011).…”