A Randomized Clinical Trial of an Inactivated Avian Influenza A (H7N7) Vaccine

<div><h3>Background</h3><p>Concern for a pandemic caused by a newly emerged avian influenza A virus has led to clinical trials with candidate vaccines as preparation for such an event. Most trials have involved vaccines for influenza A (H5N1), A (H7N7) or A (H9N2).</p> <h3>Objective</h3><p>To evaluate dosage-related safety and immunogenicity of an inactivated influenza A (H7N7) vaccine in humans.</p> <h3>Design</h3><p>One hundred twenty-five healthy young adults were randomized to receive two doses intramuscularly of placebo or 7.5, 15, 45 or 90 µg of HA of an inactivated subunit influenza A (H7N7) vaccine (25 per group), four weeks apart. Reactogenicity was evaluated closely for one week and for any adverse effect for six months after each dose. Serum hemagglutination-inhibiting and neutralizing antibody responses were determined four weeks after each dose and at six months.</p> <h3>Results</h3><p>Reactogenicity evaluations indicated the vaccinations were well tolerated. Only one subject developed a ≥4-fold serum hemagglutination-inhibition (HAI) antibody response and a final titer of ≥1∶40 four weeks after dose two and only five subjects developed a neutralizing antibody rise and a final titer of ≥1∶40 in tests performed at a central laboratory. Four of the five were given the 45 or 90 µg HA dosage. A more sensitive HAI assay at the study site revealed a dose-response with increasing HA dosage but only 36% in the 90 µg HA group developed a ≥4-fold rise in antibody in this test and only one of these achieved a titer of ≥1∶32.</p> <h3>Conclusion</h3><p>This inactivated subunit influenza A (H7N7) vaccine was safe but poorly immunogenic in humans.</p> <h3>Trials Registration</h3><p>ClinicalTrials.gov <a href="http://clinicaltrials.gov/ct2/show/NCT00546585">NCT00546585</a></p> </div

Serum Antibody Responses to H7N7 Vaccinations¹.

1<p>Hemagglutination-inhibition antibody assays at primary study 'site.</p>2<p>As determined in single redial immunodiffusion assays.</p>3<p>Number of subjects in evaluation.</p>4<p>Increasing dosage induced increased % increase; logistic regression, p = .001.</p

Solicited Adverse Events (AE) after Influenza A (H7N7) Vaccinatons.

1<p>As determined in single radial immunodiffusion assays.</p>2<p>Number subjects evaluated.</p

Demographics by Study Group.

1<p>Male vs. nonmale frequency by dosage, chi-square 1.73, p = .785.</p>2<p>White vs. nonwhite frequency by dosage, chi-square 7.04, p = .134.</p>3<p>Age vs. dosage, Anova, p>.05.</p

Serum Antibody Responses to Influenza A (H7N7) Vaccinations¹.

1<p>As determined at central laboratory; increase defined as ≥4-fold or <10 to 40.</p>2<p>As determined in single radial immunodiffusion assays.</p>3<p>Number of subjects in evaluation.</p>4<p>Hemagglutination-inhibition (HAI) and neutralizing (neut) antibody assays at central laboratory.</p

Flow diagram of the randomized clinical trial of an inactivated subunit influenza A (H7N7) vaccine.

<p>Flow diagram of the randomized clinical trial of an inactivated subunit influenza A (H7N7) vaccine.</p