By Stan Deresinski, MD, FACP, FIDSA

Clinical Professor of Medicine, Stanford University

Dr. Deresinski reports no financial relationships relevant to this field of study.

SYNOPSIS: High-dose inactivated influenza vaccine was superior to standard-dose vaccine in providing protection against influenza or pneumonia-associated hospitalizations.

SOURCE: Young-Xu Y, Van Aalst R, Mahmud SM, et al. Relative vaccine effectiveness of high-dose versus standard-dose influenza vaccines among Veterans Health Administration patients. J Infect Dis 2018 Feb 14. doi: 10.1093/infdis/jiy088. [Epub ahead of print].

Young-Xu and colleagues evaluated the relative protective efficacy of standard-dose and high-dose inactivated non-adjuvanted influenza vaccine in a retrospective cohort study that included all Veterans Health Administration patients > 65 years of age who had more than one outpatient encounter in the 2014-2015 respiratory season. The initial population evaluated consisted of 104,965 standard-dose and 125,776 high-dose vaccine recipients. After matching, these numbers were reduced to 49,091 and 24,682, respectively.

The outcomes favored the high-dose vaccine. Thus, the matched, adjusted relative vaccine efficacy was 25% (95% confidence interval [CI], 2-43%) against hospitalizations associated with influenza or pneumonia and 5% (95% CI) against influenza or pneumonia-related outpatient visits. Statistically significant benefit was not achieved with regard to influenza or pneumonia-related hospitalizations, all-cause hospitalizations or outpatient visits, or laboratory documented influenza virus infection. Thus, the high-dose vaccine appears to have modest benefit relative to the standard-dose inactivated influenza vaccine.


In their recommendations of choice of influenza vaccine for the 2017-2018 season, the Advisory Committee on Immunization Practices (ACIP) listed a bewildering array of available vaccine products.1 These included 13 vaccines in nine categories. (See Table.) Clinicians must decide among attenuated, inactivated (with or without adjuvant), and recombinant vaccines, as well as between quadrivalent and trivalent products.

The high-dose vaccine (Fluzone, High-Dose), which was first approved in 2009, contains 60 mcg of hemagglutinin, while the standard-dose vaccine contains only 15 mcg. Decisions to incorporate the high-dose vaccine into vaccine programs have had to address issues such as relative acquisition cost, concerns regarding the frequency of local adverse reactions, and inconsistent results of previous studies comparing it to standard-dose vaccine. This study, although retrospective, primarily involving male subjects, and not addressing tolerability, included a remarkably large number of subjects, and its results support the preferential use of high-dose vaccine in patients 65 years of age.


Table: Influenza Vaccine Categories

  • Inactivated, quadrivalent, standard dose
  • Inactivated, quadrivalent, standard dose, cell culture-based
  • Inactivated, quadrivalent, standard dose, intradermal
  • Inactivated, trivalent, standard dose
  • Adjuvanted, inactivated, trivalent, standard dose
  • Inactivated, trivalent, high dose
  • Recombinant, quadrivalent
  • Recombinant, trivalent
  • Live attenuated, quadrivalent


  1. Grohskopf LA, Sokolow LZ, Broder KR, et al. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices — United States, 2017-18 Influenza Season. MMWR Recomm Rep 2017;66:1-20.