A panel of IgG1 human monoclonal antibodies (HMAbs) identified by hemagglutination inhibition (HI) assay has been produced from peripheral B cells of an individual immunized with prototype H5N1 vaccine. Sequence analysis of antibody clones showed three clusters of different HMAbs as represented by HMAbs designated as BF1-1, BF1-19 and BF1-10. BF1-1 and BF1-10 have distinct CDR 1, 2 and 3 regions of both heavy and light chains. BF1-19 has the same heavy chain as BF1-1 but the light chain of BF1-10. Antibody binding affinity, KD, studies showed all three HMAbs ranging from at least about 10−8 to at least about 10−9. In vivo protection studies showed that these antibodies afforded significant protection against infection. These findings demonstrate that the antibodies of the invention are cross-neutralizing and therapeutic.