The effects of influenza traditionally have been assessed by comparing hospitalizations and deaths during an influenza season with a baseline model. These calculations suggest that seasonal influenza epidemics in the United States are responsible for between 55,000 and 431,000 hospitalizations due to pneumonia and influenza each year and as many as 49,000 deaths. The highest levels of influenza-attributable hospitalizations and deaths tend to occur in years in which H3N2 viruses predominate. Influenza vaccines confer considerable but incomplete protection and are recommended for everyone. The Advisory Committee on Immunization Practices does not endorse a specific vaccine but recommends against the live attenuated vaccine during 2016–2017 in the United States in a new Clinical Practice article.
• At what time of the year are decisions made regarding the composition of each annual influenza vaccine?
The specific influenza viruses that will be included in the vaccine each year are determined by worldwide surveillance and antigenic characterization of human viral isolates by the Global Influenza Surveillance and Response System of the World Health Organization. Currently, the production process requires that these decisions be made in February to allow for the production of vaccines to be distributed in the Northern Hemisphere in the following fall.
• Is the inactivated quadrivalent formulation of the influenza vaccine more effective than the inactivated trivalent formulation?
Since 1977, inactivated vaccines have contained three components — a recent H1N1 virus, an H3N2 virus, and an influenza B virus — in a so-called trivalent formulation (IIV3). Since approximately 1980, two antigenically distinct lineages of influenza B virus have cocirculated, and many inactivated vaccines now include both B lineages in a quadrivalent formulation (IIV4). Studies have shown that the addition of the fourth component does not interfere with the immune response to the other three components, but direct evidence of enhanced protection from IIV4, as compared with IIV3 formulations, is lacking.
Morning Report Questions
Q: Is the high-dose influenza vaccine more effective than the standard-dose vaccine?
A: Antibodies against the viral attachment protein hemagglutinin (HA) prevent entry of the virus into cells, neutralize virus in vitro, and are associated with protection in clinical studies. The serum HA-inhibition (HAI) assay is the primary means of assessing serum antibody responses to standard influenza vaccines. Higher levels of HAI antibodies are associated with increased protection against influenza, but no absolute value of antibodies uniformly predicts protection. Although the dose–response curve for IIVs is rather flat, administration of increased doses of HA protein does result in levels of postvaccination serum HAI antibodies that are higher than those with lower doses. In one very large, randomized, comparative trial, a vaccine containing approximately four times the standard dose of HA was shown to provide significantly greater protection than the standard-dose vaccine against laboratory-confirmed influenza in persons who were 65 years of age or older (incidence of influenza, 1.9% in the standard-dose group vs. 1.4% in the high-dose group). The enhanced protective effect was primarily against H3N2 viruses, the subtype with the greatest effect on older adults. Some, but not all, postmarketing studies of this high-dose vaccine (IIV3-HD) have confirmed the enhanced effectiveness of high-dose vaccine in older persons. Serious adverse events have not been more frequent with the high-dose vaccine than with the standard-dose vaccine, but pain at the injection site has been reported more often (36% vs. 24%).
Q: Have any recommendations been issued to date regarding vaccination for the 2016–2017 influenza season?
A: One live attenuated influenza vaccine (LAIV4) is licensed in the United States. LAIV is administered intranasally, and the limited replication of the vaccine viruses in the upper respiratory tract induces immunity against influenza. Observational studies have recently called into question the effectiveness of LAIV. Analysis of data collected from 2010 through 2014 showed similar levels of effectiveness of LAIV and IIV against H3N2 and B viruses, but a decreased effectiveness of LAIV, especially against H1N1 viruses in the 2010–2011 and 2013–2014 seasons. Preliminary data for 2015–2016 have also suggested minimal effectiveness of LAIV, and the Advisory Committee on Immunization Practices (ACIP) has recommended that LAIV not be used in the 2016–2017 vaccination season.