Safety and immunogenicity of a recombinant hemagglutinin vaccine for H5 influenza in humans

Recent outbreaks of avian influenza in humans have demonstrated the need fo r vaccines for influenza viruses with pandemic potential. Recombinant hemag glutinins are an attractive option for such vaccines because they do not re quire handling potentially highly pathogenic influenza viruses for vaccine production. In order to evaluate the immunogenicity, optimum dosing and tim ing of administration of a recombinant baculovirus-expressed H5 HA (rH5) in humans, 147 healthy adults were assigned randomly to receive intramuscular rH5 as two doses of 25, 45 or 90 mug each, one dose of 90 mug followed by a dose of 10 mug, or two doses of placebo, at intervals between doses of 21 , 18 or 42 days. All doses of rH5 were well tolerated. The rH5 vaccine was modestly immunogenic at high dose. Neutralizing antibody responses to a tit er of 1:80 or greater were seen in 23% (14/60) of individuals after a singl e dose of 90 mug, and in 52% (15/29) after two doses of 90 mug. Varying int ervals between doses from 21 to 42 days had no significant effect on antibo dy responses to vaccination. These results suggest that baculovirus-express ed H5 HA can induce functional antibody in individuals who have not had pri or exposure to H5 viruses, but that further studies to improve the immunoge nicity of the vaccine are needed. (C) 2001 Elsevier Science Ltd. All rights reserved.