Influenza Spotlight

Study Shows Adjuvanted Influenza Vaccination More Effective

Influenza vaccination for older adults is highly recommended because influenza is associated with a significant increase in all-cause mortality and risk of hospitalization. However, the effectiveness of influenza vaccination decreases with advancing age. Immunogenicity studies show that the oil-in-water emulsion MF59 adjuvanted influenza vaccine may boost effectiveness more than an unadjuvanted vaccine, but this mechanism of action is not well understood. A recent Canadian study published in PLoS One sought to compare the effectiveness of adjuvanted and unadjuvanted influenza vaccines with no vaccination in a cohort of 282 elderly persons, approximately half of whom resided in a long-term care facility (www.ncbi.nlm.nih.gov/pubmed/23933368).

Participants were included in the case-controlled study if they were aged 65 years or older (more than half were aged 85 years or older), had influenza-like symptoms, had no immunodeficiency conditions, and had laboratory-confirmed influenza (A[H1N1)pdm09) and/or pneumonia. Study participants were classified as “vaccinated” if they had received a dose of the influenza vaccine at least 14 days before the onset of symptoms or as “not vaccinated” if they received no vaccination or received the first dose of vaccination within 14 days of the onset of symptoms. All vaccines contained the recommended strains for the Northern Hemisphere for the 2011-2012 flu season, which included the A/California/7/2009 (H1N1)-like virus, A/Perth/16/2009 (H3N2)-like virus, and B/Brisbane/60/2008-like virus.

Cases (n=84) were defined as patients whose respiratory sample was influenza-positive, and controls (n=198) were defined as patients whose respiratory sample was influenza-negative but met a clinical definition of influenza-like illness. Of the total number of participants, 81% (n=221) were vaccinated: 73% received the adjuvanted vaccine and 27% received the unadjuvanted vaccine. Which vaccine was given was determined by external factors, such as the health authority and availability.

The results of the multivariate analysis, which controlled for age, sex, long-term care residency, and chronic conditions, showed unadjuvanted vaccines to be ineffective in all groups except in noninstitutionalized persons. The effectiveness of the adjuvanted vaccine was 58% (P<.04), with a much higher rate of effectiveness in noninstitutionalized patients (72%; P=.047). The univariate analysis showed the effectiveness of unadjuvanted vaccine to be at 42%, but this finding did not reach statistical significant (P=.30). Based on these findings, the authors concluded, “Adjuvanted vaccine is not a panacea in elderly persons with immunosenescence, with a standardized vaccine effectiveness in this study of about 60%. However, [unadjuvanted vaccine] was ineffective in the same group this year and adjuvanted vaccine appeared to be a significant improvement on the protection available against the known hospitalizations and death in this group.”

Fluzone High-Dose Vaccine Is Clinically Superior to the Standard Dose in Older Adults

Fluzone High-Dose vaccine is the only FDA-approved influenza vaccine with a specific indication for people aged 65 years and older. Approved in 2009, Fluzone High-Dose intramuscular injection protects against influenza caused by virus subtypes A and B. The approval was based on data from the vaccine’s phase 3 clinical trial that showed Fluzone High-Dose to have superior efficacy in the older adult population compared with the standard-dose Fluzone vaccine.

On August 28, 2013, Fluzone manufacturer Sanofi Pasteur announced the results of an efficacy trial that reaffirms these findings. In the study, Fluzone High-Dose was 24.2% more effective than standard-dose Fluzone vaccine in preventing influenza in more than 30,000 participants aged 65 years and older. Additionally, the results showed that Fluzone High-Dose delivered consistent clinical benefit across influenza virus types, clinical illness definitions, and laboratory methods of confirming influenza diagnosis.

“Influenza vaccines have been shown to offer public health benefits in preventing influenza and its complications in all age groups; however, older adults still have the highest rates of influenza-related hospitalization and death despite having high immunization rates,” said Sanofi Senior Vice President of Research and Development John Shiver in a press release.

Sanofi said it would submit a full clinical study report to the FDA by early 2014 and will seek modification to the label of Fluzone High-Dose to indicate superior efficacy data in older adults. Future trials will be conducted to determine the effectiveness of Fluzone High-Dose against different influenza strains. For more information about Fluzone High-Dose, visit www.fluzone.com/health-care-professionals/fluzone-high-dose-vaccine.cfm.

Influenza Vaccination Likely Has Protective Effect in Prevention of Myocardial Infarction

There is much epidemiological evidence to suggest a link between influenza and acute myocardial infarction (AMI) due to the high rate of all-cause mortality and cardiovascular hospitalizations of older adults during influenza season; however, there is a lack of direct evidence that influenza causes ischemic events. The results of a case-controlled study show that although influenza cannot predict AMI, influenza vaccination may significantly lower an older adult’s risk of AMI. In a study supported by GlaxoSmithKline, a team of Australian investigators enrolled 275 inpatients with AMI from a tertiary referral hospital (cases) and 284 outpatients without AMI (controls). All patients were aged 40 years or older. The primary and secondary study outcomes were laboratory evidence of influenza and baseline acute respiratory tract infection (ARTI), respectively. Half of the total study population reported being vaccinated within the year of recruitment.

The investigators found undiagnosed influenza in 10% of the total study group (12.4% of cases, n=34; 6.7% controls, n=19). ARTI was self-reported in 22% of vaccinated patients and in 27% of unvaccinated patients. The unadjusted analysis showed that influenza and ARTI significantly predicted AMI. However, in the multivariate analysis, influenza infection was not considered a significant predictor of AMI, yet influenza vaccination was still significantly protective, with an estimated vaccine effectiveness for prevention of AMI at 45% in patients between the ages of 40 and 64 years and 33% in patients aged 65 years and older. Although the investigators could not demonstrate a direct effect of influenza infection on AMI, based on these findings, they concluded, “At least, clinicians should be aware of influenza and infection as an underlying and poorly diagnosed precipitant or comorbidity in hospitalized patients and of the preventive benefit of influenza vaccine for patients at risk for AMI.” The results of the study were published in August online ahead of print in Heart (www.ncbi.nlm.nih.gov/pubmed/23966030).