Cross-Reactive Anti-Avian H5N1 Influenza Neutralizing Antibodies in a Normal ‘Exposure-Naïve’ Australian Blood Donor Population

It is necessary to understand whether some humans possess natural humoral-immune protection for avianH5N1 influenza. To broadly assess an exposure naïve cohort we have examined intravenous immunoglobulins (IVIGs) isolated from pools of many thousands of normal Australian blood donations. In studies of the anti-H5N1 antibody potential of these highly purified IVIG therapeutics and of individual donor sera we have identified antibodies that bind to both H5N1 surface envelope and internal viral proteins and neutralize in vitro MDCK and Vero cell infections by highly pathogenic avian influenza clade I and II and human-derived H5N1 isolates. As this reactivity is removed by adsorption with purified H3N2 and H1N1 strains, anti-H5N1 cross-reacting hetero-typic antibodies are implicated. These findings support that some individuals do contain low levels of specific and neutralizing anti-H5N1 antibodies. The protective relevance of this in vivo remains yet to be determined.