Background Influenza A (H5N1) viruses could cause a severe worldwideepidemic, with high attack rates, large numbers of deaths andhospitalizations, and wide disruption. Effective vaccines againstthese viruses in humans are urgently needed.
Methods We conducted a multicenter, double-blind two-stage studyinvolving 451 healthy adults 18 to 64 years of age who wererandomly assigned in a 2:2:2:2:1 ratio to receive two intramusculardoses of a subvirion influenza A (H5N1) vaccine of 90, 45, 15,or 7.5 µg of hemagglutinin antigen or placebo. The subjectswere followed for the safety analysis for 56 days. Serum samplesobtained before each vaccination and again 28 days after thesecond vaccination were tested for H5 antibody by microneutralizationand hemagglutination inhibition.
Results Mild pain at the injection site was the most commonadverse event for all doses of vaccine. The frequency of a serumantibody response was highest among subjects receiving dosesof 45 µg or 90 µg. Among those who received twodoses of 90 µg, neutralization antibody titers reached1:40 or greater in 54 percent, and hemagglutination-inhibitiontiters reached 1:40 or greater in 58 percent. Neutralizationtiters of 1:40 or greater were seen in 43 percent, 22 percent,and 9 percent of the subjects receiving two doses of 45, 15,and 7.5 µg, respectively. No responses were seen in placeborecipients.
Conclusions A two-dose regimen of 90 µg of subvirion influenzaA (H5N1) vaccine does not cause severe side effects and, inthe majority of recipients, generates neutralizing antibodyresponses typically associated with protection against influenza.A conventional subvirion H5 influenza vaccine may be effectivein preventing influenza A (H5N1) disease in humans. (ClinicalTrials.govnumber, NCT00115986
[ClinicalTrials.gov]
.)
Source Information
From the Department of Medicine, University of Rochester, Rochester, N.Y.(J.J.T.); the Center for Vaccine Development, University of Maryland School of Medicine, Baltimore (J.D.C.); the Los Angeles Biomedical Research Institute and UCLA Center for Vaccine Research, HarborUCLA Medical Center, Los Angeles (K.M.Z.); Southern Research Institute, Birmingham, Ala. (T.R.); and EMMES, Rockville, Md. (M.W.).
Address reprint requests to Dr. Treanor at the Department of Medicine, University of Rochester Medical Center, 601 Elmwood Ave., Rm. 3-6309, Rochester, NY 14642, or at john_treanor{at}urmc.rochester.edu.
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