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Previous Volume 354:1343-1351 March 30, 2006 Number 13 Next

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ABSTRACT

Background Influenza A (H5N1) viruses could cause a severe worldwide epidemic, with high attack rates, large numbers of deaths and hospitalizations, and wide disruption. Effective vaccines against these viruses in humans are urgently needed.

Methods We conducted a multicenter, double-blind two-stage study involving 451 healthy adults 18 to 64 years of age who were randomly assigned in a 2:2:2:2:1 ratio to receive two intramuscular doses of a subvirion influenza A (H5N1) vaccine of 90, 45, 15, or 7.5 µg of hemagglutinin antigen or placebo. The subjects were followed for the safety analysis for 56 days. Serum samples obtained before each vaccination and again 28 days after the second vaccination were tested for H5 antibody by microneutralization and hemagglutination inhibition.

Results Mild pain at the injection site was the most common adverse event for all doses of vaccine. The frequency of a serum antibody response was highest among subjects receiving doses of 45 µg or 90 µg. Among those who received two doses of 90 µg, neutralization antibody titers reached 1:40 or greater in 54 percent, and hemagglutination-inhibition titers reached 1:40 or greater in 58 percent. Neutralization titers 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 placebo recipients.

Conclusions A two-dose regimen of 90 µg of subvirion influenza A (H5N1) vaccine does not cause severe side effects and, in the majority of recipients, generates neutralizing antibody responses typically associated with protection against influenza. A conventional subvirion H5 influenza vaccine may be effective in preventing influenza A (H5N1) disease in humans. (ClinicalTrials.gov number, 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, Harbor–UCLA 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.

Full Text of this Article

Related Letters:

An Inactivated Subvirion Influenza A (H5N1) Vaccine
Johansson B. E., Brett I. C., Focosi D., Poland G. A.
Extract | Full Text | PDF  
N Engl J Med 2006; 354:2724-2725, Jun 22, 2006. Correspondence

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