Source: DGNews  |  Posted 3 years ago

By Crina Frincu-Mallos, PhD

WASHINGTON, DC -- May 8, 2008 -- A high dose of an influenza virus vaccine has been shown to have superior immunogenicity than the standard dose of the vaccine, researchers reported here at the 2008 American Geriatrics Society (AGS) Annual Scientific Meeting.

Vaccination elicits a lower antibody response in the elderly population compared with younger adults. Therefore, improvement of the immune response to influenza vaccination in the elderly, who are at higher risk for influenza-related morbidity and mortality, represents an important goal.

To address this issue, a high-dose trivalent inactivated split-virion influenza vaccine was developed and tested in this patient population, according to the researchers.

Lead author Ann R. Falsey, MD, Associate Professor of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, and her collaborators sought to evaluate the protective efficacy of high-dose influenza virus vaccine compared with standard-dose vaccine.

The high-dose regimen tested contained haemagglutinin 60 mcg per strain, while the licensed standard-dose regimen contained haemagglutinin 15 mcg per strain, said the researchers.

This multicentre, randomised, double-blind, active-controlled, phase 3 study accrued 2,575 subjects in the high-dose vaccine arm and 1,262 subjects in the standard-dose arm, explained Dr. Falsey in a poster presentation on May 2. Women made up 51.3% of the cohort in the high-dose arm and 54.6% in the standard-dose arm. Mean age was 73 years (range, 65-97 years).

The vaccines were administered as a single intramuscular injection (0.5 mL).

Looking at the immunogenicity results, the high dose elicited better antibody responses in 2 influenza A strains (H1N1 and H3N2) and in the influenza B strain, explained Dr. Falsey.

At 28 days postvaccination, the geometric mean titres (GMTs) for the H1N1 A strain were 116 for subjects treated with the high dose compared with 67 for those treated with the standard dose, resulting in a ratio of GMT of 1.7 (P < .0001).

Similarly, at 28 days postvaccination, the GMTs for the H3N2 A influenza strain were 609 for the high-dose vaccine and 332 for the standard dose, resulting in a ratio of GMTs of 1.8 (P < .0001).

These results show that the high dose is more efficacious for each A strain in this patient population, noted Dr. Falsey.

However, in the B influenza strain, the high dose vaccine did not produce a statistically significant improvement over the standard dose. At 28 days postvaccination, the GMTs for the B strain were 69 for subjects treated with the high-dose influenza vaccine and 52 for the standard dose, resulting in a GMTs ratio of 1.32 (P < .0001). This finding, Dr. Falsey said, indicates that the high dose is only slightly more efficacious than the standard dose.

Seroprotection, defined as the percentage of subjects with GMTs >1.4 was higher for the high dose than the standard dose for all strains -- 90% versus 77% for the H1N1 A strain, 99% versus 97% for the H3N2 A strain, and 79% versus 68% for the B strain.

The investigators reported no safety concerns. However, there were more local reactions with the high-dose vaccine (54%) versus the standard dose (44%), but all were transient and mild to moderate.

Funding for this study was provided by sanofi-pasteur.

[Presentation title: Superior Immunogenicity of High Dose Influenza Vaccine in Adults Aged >=65 Years. Abstract D133]