High-dose flu vaccine may work better in elderly people

A high-dose flu vaccine induced significantly higher antibody responses and provided better protection against laboratory-confirmed influenza than did its standard-dose counterpart among persons 65 years of age or older, an industry-funded study found.

The high-dose version of a trivalent, inactivated flu vaccine (Fluzone High-Dose) contains 4 times as much hemagglutinin (60 μg per strain) as the standard dose (Fluzone, 15 μg per strain). It was licensed for use in the United States in December 2009 with a requirement to show clinical benefit. Researchers conducted a phase IIIb-IV, multicenter, randomized, double-blind, active-controlled trial to compare relative efficacy, effectiveness, safety (serious adverse events), and immunogenicity (hemagglutination-inhibition titers) during the 2011-2012 and the 2012-2013 flu seasons. The study was funded by Sanofi Pasteur, which makes both vaccines.

Results appeared in the Aug. 14 New England Journal of Medicine.

The study enrolled 31,989 people ages 65 or older from 126 research centers in North America; 15,991 received the high-dose vaccine, and 15,998 received the standard dose. In the intention-to-treat analysis, 228 participants in the high-dose group (1.4%) and 301 participants in the standard dose group (1.9%) had laboratory-confirmed flu and accompanying illness (relative efficacy, 24.2%; 95% CI, 9.7% to 36.5%). Relative vaccine efficacy against laboratory-confirmed, flulike illness caused by similar strains of the flu was 35.4% (95% CI, 12.5% to 52.5%).

During the safety surveillance period of 6 to 8 months after vaccination, 1,323 participants (8.3%) in the high-dose group and 1,442 participants (9.0%) in the standard-dose group had at least 1 serious adverse event. The relative risk for having at least 1 serious adverse event with the high-dose vaccine, as compared with the standard dose, was 0.92 (95% CI, 0.85 to 0.99).

Three high-dose recipients had serious adverse events related to vaccination: cranial-nerve VI palsy starting 1 day after vaccination, hypovolemic shock associated with diarrhea starting 1 day after vaccination, and acute disseminated encephalomyelitis starting 117 days after vaccination. All 3 events resolved before the end of the study, and none resulted in discontinuation from the study. There were no serious events among standard-dose recipients.

The researchers noted that the relative efficacy shows that about one-quarter of all breakthrough flus could be prevented if the high-dose vaccine were used instead of the standard-dose version and that more than a third of breakthrough flus caused by strains similar to the vaccine could be prevented.

“Since influenza infections with type A (H3N2) viruses are considered more burdensome than other viral types and subtypes in older adults, it is expected that a benefit of IIV3-HD [the high-dose version] in this population will remain even in the context of quadrivalent standard-dose vaccines,” the authors wrote.

In other flu news, the CDC's Advisory Committee on Immunization Practices (ACIP) released its recommendations for the 2014-2015 flu season on Aug. 15. They are available online.