We analyzed the ability of a vaccine vector based on vesicular stomatitis virus (VSV) to induce a neutralizing antibody (nAb) response to avian influenza viruses (AIV) in rhesus macaques. Animals vaccinated with vectors expressing either the A/Hong Kong/156/1997 or A/Vietnam/1203/2004 H5 hemagglutinin (HA) were able to generate robust nAb responses. The ability of the vectors to induce nAbs against homologous and heterologous AIVs after a single dose was dependent upon the HA antigen incorporated into the VSV vaccine. The vectors expressing the A/Vietnam/1203/2004 H5 HA were superior to those expressing the A/Hong Kong/156/1997 HA at inducing cross-clade nAbs