High-Dose Flu Vaccine More Effective than Standard Dose


Benefits from HD-IIV might be greater for protection against influenza B/Yamagata and influenza A(H3N2) than for influenza A(H1N1) pdm09.


In a comparison between standard- and high-dose influenza (flu) vaccines, high-dose offered greater effectiveness for the prevention of influenza hospitalization among adults aged >65 years old, according to recent study findings.

Joshua Doyle, MD, PhD, and a team of investigators enrolled hospitalized patients with acute respiratory illness to evaluate the effectiveness of high-dose inactivated influenza vaccine (HD-IIV) and standard-dose influenza vaccines (SD-IIV) for prevention of influenza-associated hospitalizations. The findings, though not statistically significant, suggested that benefit from HD-IIV might be greater for protection against influenza B/Yamagata and influenza A(H3N2) than for influenza A(H1N1) pdm09.

Doyle, from the Influenza Division at the National Center for Immunization and Respiratory Diseases at the US Centers for Disease Control and Prevention (CDC), included 1400-plus patients >65 years old who were hospitalized at 1 of 8 hospitals in the United States Hospitalized Adult Influenza Vaccine Effectiveness Network during the 2015-2016 and 2016-2017 flu seasons. Patients who were enrolled were tested for flu, and receipt of vaccine by type was recorded.

Each participant provided information on demographics, comorbidities, and flu vaccination status. Clinical course information was obtained by the investigators through the patient’s electronic health record (EHR).

Patients were considered vaccinated if the date of their vaccination was >14 days prior to illness onset. The investigators excluded patients whose self-reported vaccination was unverified after review or if they were vaccinated 0-13 days before illness onset.

The team estimated vaccine effectiveness by comparing the odds of the flu among vaccinated and unvaccinated patients.

Among the 1487 patients included, 1107 (74%) were vaccinated. Those who were >75 years old, white, and had greater comorbidity were more likely to be vaccinated (P <.05 for each). Patients with prior season vaccination were also more likely to be vaccinated (P <.001). Individuals who smoked tobacco were less likely to be vaccinated (P <.001).

Nearly 500 patients (44%) received SD-IIV (21% SD-IIV3; 79% SD-IIV4) and 622 (56%) received HD-IIV). Those who received the HD-IIV3 vaccine were more likely to be >75 years old; enrolled in 2016-2017 or at the Pennsylvania or Tennessee hospitals; have chronic obstructive pulmonary disease (COPD) or metabolic disorders; and to have been vaccinated at pharmacies, grocery stores, or workplaces.

Of the patients who tested positive for flu, 24% were unvaccinated, 18% had SD-IIV, and 16% received HD-IIV (P = .003). Those who tested positive were more likely to be non-white males, enrolled at the Pennsylvania site, and among patients with lesser frailty (P <.05 for each).

Vaccine effectiveness for any vaccination was 21% (95% CI, -15 to 46), 6% (95% CI, -42 to 38) for SD-IIV, and 32% (95% CI, -3 to 54) for HD-IIV for all flu types and subtypes. Relative effectives of HD-IIV compared to SD-IIV was 27% (95% CI, -1 to 48).

Effectiveness against flu A(H1N1)pdm09 was 30% (-54 to 68) for any vaccine, 23% (95% CI, -84 to 68) for SD-IIV, and 36% (95% CI, -54 to 74) for HD-IIV. Relative vaccine effectiveness was 17% (95% CI, -76 to 61). Against flu A(H3N2), effectiveness was 8% (−54 to 45) for any vaccine, −6% (95% CI, −86 to 40) for SD-IIV, and 18% (95% CI, −42 to 53) for HD-IIV, with a relative effectiveness of 23% (95% CI, −19 to 50).

For flu B/Yamagata, vaccine effectiveness was 50% (95% CI, −1 to 75) for any vaccine, 31% (95% CI, −50 to 68) for SD-IIV, and 62% (95% CI, 16-83) for HD-IIV. Relative effectiveness was 44% (95% CI, −13 to 73).

Additional evaluation of HD-IIV could help investigators better understand differences in relative benefit of the vaccine across studies, seasons, and flu subtypes, the study investigators wrote. But evidence suggested that the vaccine could provide improved protection against serious illness and its consequences among the large and vulnerable elderly population.

The study, “Relative and absolute effectiveness of high-dose and standard-dose influenza vaccine against influenza-related hospitalization among older adults — United States, 2015-2017,” was published online in the journal Clinical Infectious Diseases.

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