Protective efficacy of combined live intranasal and inactivated influenza A virus vaccines in the elderly.

OBJECTIVE: To evaluate the efficacy of adding intranasal live attenuated cold-adapted influenza A vaccine to inactivated influenza vaccine to prevent influenza A in elderly residents of long-term-care institutions. DESIGN: Randomized, double-blind, placebo-controlled study conducted over 3 years. SETTING: Three large nursing homes. PARTICIPANTS: A total of 523 residents of nursing homes (mean age, 84.2 years). INTERVENTIONS: All participants received trivalent inactivated influenza vaccine parenterally and were randomly assigned to receive either live attenuated influenza A (H3N2) virus vaccine or placebo intranasally. MEASUREMENTS: Laboratory-documented influenza A was defined as a respiratory illness plus isolation of influenza A virus from nasal secretions, significant serologic response, or both. Participants were considered to have been exposed to influenza A if they resided in an institution in which cases of influenza A were documented. Outbreak-associated illnesses were defined as those occurring between the first and last isolation of influenza virus from within the institution, +/- 3 days. RESULTS: Participants who received intranasal vaccine and were subsequently exposed to influenza A had significantly lower rates of laboratory-documented influenza A (9 of 162 vaccine recipients compared with 24 of 169 placebo recipients; vaccine protective efficacy, 60.6%; 95% CI, 18% to 82%), outbreak-associated respiratory illnesses (13 of 162 vaccine recipients compared with 34 of 169 placebo recipients; vaccine protective efficacy, 56.8%; CI 23% to 76%), and outbreak-associated influenza-like illnesses (6 of 162 vaccine recipients compared with 18 of 169 placebo recipients; vaccine protective efficacy, 65.0%; CI 17% to 86%). CONCLUSIONS: Intranasal immunization with live attenuated influenza A virus vaccine provided additional protection against influenza A when added to parenteral trivalent inactivated influenza vaccine among elderly nursing home residents.