Evaluation of a single dose of half strength inactivated influenza vaccine in healthy adults
Introduction
The most effective tool currently available for control of influenza is annual administration of inactivated influenza vaccine. Vaccination is particularly recommended for use in individuals at high-risk for influenza-related complications [1], but it is also recommended for healthy adults in a variety of situations. It is estimated that approximately 50 million doses of vaccine were administered, to high-risk adults in the US in 1999–2000, and that at least 70 million doses would be needed to vaccinate all high-risk individuals in the US.
Delays in production of the 2000–2001 inactivated influenza vaccine in the US caused significant concern that the number of available doses would not be sufficient to support vaccine use at the desired level. Eventually, sufficient quantities of vaccine were produced to meet demand. However, contingency planning is needed for similar situations in the future because the yield of influenza viruses in vaccine production varies with the strain and is not entirely predictable.
One strategy to increase the number of persons who could be immunized, in a situation of critical shortage of vaccine would be to administer a lower dose of vaccine to some groups. Currently, trivalent inactivated influenza vaccines are given intramuscularly to adults as a 0.5 ml dose that is standardized to contain at least 15 μg of each hemagglutinin as measured by single radial immunodiffusion (SRID) [2]. The relatively few studies available regarding the immunogenicity, of lower doses of modern influenza vaccines suggest that doses of 5–10 μg of hemagglutinin are only slightly less immunogenic than are doses of 15–20 μg in adults, who have been primed by previous infection or vaccination [3], [4], [5], [6].
We conducted the current study, in order to obtain more information on the safety and immunogenicity of lower dose influenza vaccine. Since the most likely group in whom a low dose strategy would be implemented would be individuals who normally respond well to vaccination, the focus of this evaluation was on healthy young adults. The primary outcome measure was the development of hemagglutination-inhibiting antibody, a simple measure of functional antibody that correlates with protection [7].
Section snippets
Study design
The study was conducted as a prospective, multicenter, randomized, open-label trial. Eligible participants were stratified into two groups based on self-reported history of previous receipt of inactivated influenza vaccine within the past 3 years, individuals reporting vaccination within the last 3 years and those reporting no such vaccination. Subjects within each group were randomized to receive a single dose of either 0.5 or 0.25 ml of trivalent inactivated influenza vaccine by intramuscular
Results
A total of 1009 subjects were enrolled in this study during the 2-week-period between 9 and 23 August 2000, including 569 subjects who reported vaccination in the last 3 years and 440 subjects who did not. Among previously vaccinated subjects, 283 were randomized to the half dose group and 286 to full dose. Among those who had not been vaccinated previously, 220 subjects were randomized to the half dose and 220 to the full dose. Three subjects, all in the half dose group, did not complete the
Discussion
Several trials evaluating the dose-dependent immune response to inactivated influenza vaccines were conducted in the years immediately following the emergence of H1N1 influenza viruses in the late 1970s. These trials, which also utilized whose HA content was quantified by SRID, generally showed an increased frequency and magnitude of responses at higher (∼20 μg HA) than lower (∼7 μg HA) doses of HA antigen [3], [4], [5], [6]. However, these differences were small and not seen in all studies.
Acknowledgements
The authors would like to thank Nancy Cox, Joel Ward, Robert Edelman, Mark Van Raden and Bill Blackwelder for critical advice in study design and review of the manuscript, and acknowledge the efforts of the following individuals in the conduct of the study: Inger Baker, JoAnna Becker, Renee Bellrichard, Nanette Bond, Pat Chatfield, Jeanne Comstock, Carol Farnworth, Jocelyn Guevarra, Henrietta Hall, Amy Hoeper, Patricia Koops, Tracey Liddell, Stephen Lindstrom, Teresa Liu, James Love, Jonathan
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