Capua, J

Capua, J. a mouse model. Antigenicity studies using ferret antibodies raised against H7N2-PR8 indicated that this virus confers broad cross-reactivity with divergent H7 viruses of different years and lineages. Mice and chickens inoculated with high doses of H7N2-PR8 supported virus replication but survived, indicating that this virus is comparable to ARV-825 other avian viruses of low pathogenicity. To assess the protective efficacy of H7N2-PR8, mice were immunized with two doses of formalin-inactivated H7N2-PR8, alone or with alum. Vaccinated mice subsequently challenged with highly pathogenic viruses from homologous and heterologous lineages A/Canada/444/04 (H7N3) and A/Netherlands/219/03 (H7N7) showed pronounced reduction of wild-type virus replication. These studies indicate that H7N2-PR8 is immunogenic, safe, and protective in animal models; these are the essential attributes to qualify for phase I human clinical trials as a prepandemic vaccine. Influenza A viruses are enzootic among wild waterfowl (36). Viruses of the H5 and H7 subtypes can mutate from low to high pathogenicity after introduction into domestic poultry (2, 12, 29, 35). The high virulence of H5 and H7 viruses from poultry is generally contingent on the insertion of nucleotides in the hemagglutinin (HA) gene that encode basic amino acids at the cleavage site of HA0. This change renders HA cleavable by ubiquitous host cell proteases and facilitates systemic virus spread (3). Recent outbreaks of H7 avian influenza in poultry have been associated with sporadic transmission to humans. In 2003, an outbreak of highly pathogenic avian influenza virus (subtype H7N7) in commercial poultry in The Netherlands resulted in transmission to people involved in poultry handling. Although most infected individuals developed only mild influenza-like symptoms, one individual developed acute respiratory distress syndrome and died (9, 14). In 2004, an outbreak of a highly pathogenic H7N3 occurred in poultry in Canada, infecting two humans that had close contact with poultry. Both patients developed conjunctivitis and influenza-like illness, which improved after oseltamivir therapy (23). These incidents and the current H5N1 outbreaks in Asia, Europe, and Africa have raised concerns about potential pandemics caused by viruses of the H7 subtype or by some other avian influenza viruses with the potential to be transmitted to humans and have advertised global preparedness to prevent such events (20, 21). For this reason, different H5N1 and H7N7 vaccine candidates have been prepared to meet up with pandemic preparedness goals (8, 22, 30, 31). Viruses of the H5 and H7 subtypes have caused outbreaks in commercial poultry in the Americas (1, 7, 11, 16, 17). These viruses constitute a lineage that is genetically and antigenically unique from your Western and Asian lineages which currently circulate in that hemisphere. Molecular analysis of multiple H7N2 isolates from outbreaks in U.S. poultry exposed that their HA genes are most closely related to the ones that have been C13orf1 circulating in live-bird ARV-825 markets in the northeastern United States since 1996 (28). Recent studies possess indicated that, in these viruses, the HA cleavage site sequence is definitely progressing toward a cleavage site sequence that fulfills the criteria established for highly pathogenic strains (27). An outbreak of low-pathogenicity H7N2 avian influenza disease in turkey farms in Virginia resulted in the damage of over 4.7 million birds (1). During this outbreak, one poultry worker reported a top respiratory illness that was later on found to be associated with H7N2 illness (4). An independent case of influenza-like illness caused by H7N2 occurred in 2003 in New York (5), but the source of this illness was not identified. Evidence of H7 avian influenza disease illness in humans shows that the constant blood circulation of H7N2 viruses in poultry constitutes a ARV-825 potential threat to.