Trial to Compare the Safety, Tolerability, and Efficacy of Influenza Virus Vaccine, (CAIV-T) With Inactivated, Influenza Vaccine, Trivalent, Types A & B, in Adults Aged 60 Years and Older Against Culture-confirmed Influenza (FluMist)

• The first episode of a culture-confirmed influenza-illness, caused by any community-acquired subtype, which occurs at least 15 days following receipt of a dose of study vaccine. [ Time Frame: 15 days after dosing through 30Nov2002 ] [ Designated as safety issue: No ]
  The criteria for obtaining nasal and throat swabs for viral culture were any one of the following: A feeling of "feverishness", An oral temperature ≥37.2ºC, Sore throat, New or increased cough, Malaise, Myalgia. Swabs for viral cultures were also obtained, if, in the opinion of the investigator, the symptom complex so warranted.
• The first episode in a study subject of a culture-confirmed influenza illness caused by community-acquired virus of each of the subtypes antigenically similar to those contained in the vaccine [ Time Frame: 15 days after dosing through 30Nov2002 ] [ Designated as safety issue: No ]
  The criteria for obtaining nasal and throat swabs for viral culture were any one of the following: A feeling of "feverishness", An oral temperature ≥37.2ºC, Sore throat, New or increased cough, Malaise, Myalgia. Swabs for viral cultures were also obtained, if, in the opinion of the investigator, the symptom complex so warranted.
• The first episode in a study subject of a culture-confirmed influenza illness caused by any community-acquired virus of each of the subtypes. [ Time Frame: 15 days after dosing through 30Nov2002 ] [ Designated as safety issue: No ]
  The criteria for obtaining nasal and throat swabs for viral culture were any one of the following: A feeling of "feverishness", An oral temperature ≥37.2ºC, Sore throat, New or increased cough, Malaise, Myalgia. Swabs for viral cultures were also obtained, if, in the opinion of the investigator, the symptom complex so warranted.
• The first episode of influenza-like illness [ Time Frame: 15 days after dosing through 30Nov2002 ] [ Designated as safety issue: No ]
• Incidence of clinic visits [ Time Frame: 15 days after dosing through 30Nov2002 ] [ Designated as safety issue: No ]
  A possibility of multiple visits per subject; each visit will be counted once in the analysis.
• Incidence of hospitalization [ Time Frame: 15 days after dosing through 30Nov2002 ] [ Designated as safety issue: No ]
• Incidence of confirmed pneumonia [ Time Frame: 15 days after dosing through 30Nov2002 ] [ Designated as safety issue: No ]
  Pneumonia means one or more areas of acute interstitial or alveolar infiltrates documented radiographically
• Incidence of death due to influenza-like illness [ Time Frame: 15 days after dosing through 30Nov2002 ] [ Designated as safety issue: No ]
  With or without confirmation by viral culture or PCR analysis
• Incidence of seroconversion [ Time Frame: Day 0-35 ] [ Designated as safety issue: No ]
  Seroconversion is defined as at least a 4-fold increase in titer from baseline to the sample 35 plus or minus 7 days after vaccination. all subjects were to provide serum samples at 2 time points: at study visit 1 prior to vaccination with CAIV-T or TIV, and 35 days ± 7 days following vaccination (study visit 2).
• Incidence of systemic reactogenicity events [ Time Frame: Day 0-10 ] [ Designated as safety issue: Yes ]
  The 12 systemic reactions were fever with 3 grades defined as ≥37.2°C, ≥38.6°C, and ≥40°C based on the temperature reported on the diary card in addition to the 9 events reported on the diary card.
• Incidence of local reactions [ Time Frame: Days 0-10 ] [ Designated as safety issue: Yes ]
  The local reactions were pain, redness (2 grades: any and significant), and swelling (also 2 grades).
• Incidence of adverse events [ Time Frame: Days 0-10 ] [ Designated as safety issue: Yes ]

To demonstrate that the efficacy over a defined surveillance period against culture-confirmed influenza-illness caused by community-acquired subtypes antigenically similar to those contained in the vaccine, in adults aged at least 60 years at enrollment, of a single intranasally (IN) -administered dose of a liquid formulation of influenza virus vaccine,(CAIV-T) is non inferior compared with that of a single dose of commercially available influenza vaccine inactivated (TIV) administered intramuscularly (IM) prior to the anticipated commencement of the influenza season.

• Biological: Cold-adapted influenza vaccine trivalent (CAIV-T)
  Liquid CAIV-T vaccine for this study consisted of 3 cold-adapted, attenuated, reassortant strains, representing the HA and NA antigens of the A/New Caledonia/20/99 (H1N1), A/Panama/2007/99 (H3N2), and B/Victoria/504/2000 influenza strains. The vaccine contained no preservatives and had a pH of 7.2 ± 0.5.
  Other Name: FluMist
• Biological: Trivalent Inactivated Vaccine (TIV)
  Commercially available TIV, inactivated influenza vaccine (Split Virion) BP (Aventis Pasteur MSD, Lyon, France) was administered IM according to the manufacturer's dosing instructions (one 0.5-mL IM dose for adults).

• Experimental: Cold-adapted influenza vaccine trivalent (CAIV-T)
  A single 0.2 mL dose of 10^7 fluorescent focus units was administered intranasally.
  Intervention: Biological: Cold-adapted influenza vaccine trivalent (CAIV-T)
• Active Comparator: Trivalent Inactivated Vaccine (TIV)
  A single dose was administered by intramuscular injection.
  Intervention: Biological: Trivalent Inactivated Vaccine (TIV)

Inclusion Criteria:

• who are aged at least 60 years or older at the time of enrollment;
• who are determined by medical history, physical examination and clinical judgement to be eligible for this study;
• who have provided written informed consent after the nature of the study has been explained;
• who will be available for duration of the trial (from enrollment to November 30th, 2003);
• who can be reached by study staff for the post-vaccination and weekly surveillance contacts [telephone, clinic or home visit].

Exclusion Criteria:

• who are perceived to be unavailable or difficult to contact for evaluation or study visits during the study period;
• who are a resident of a nursing home or long-term care facility or other institution receiving skilled or semi-skilled nursing care (refer to Influenza study specific manual). An ambulatory subject who is a resident of a retirement home or village is eligible for the trial;
• with any signs of renal insufficiency requiring supportive therapy or progressive neurological disease. (Subjects with other stable pre-existing disease, defined as disease not requiring change in therapy or hospitalization within 12 weeks before receipt of study vaccination will be eligible).
• with evidence of dementia or other severe cognitive impairment based on Mini Mental State Examination (MMSE) scores (refer to Influenza study specific manual);
• with a known or suspected disease of the immune system or those receiving immunosuppressive therapy, including systemic corticosteroids; or cytotoxic agents;
• who received any blood products, including immunoglobulin, in the period from six months prior to vaccination through to the conclusion of the study;
• have an immunosuppressed or an immunocompromised individual living in the same household;
• with a documented history of hypersensitivity to egg or egg protein or any other component of the CAIV-T or TIV vaccine;
• who were administered any live virus vaccine within one month prior to vaccination or expected to receive another live virus vaccine within one month of vaccination in this study;
• for whom there is intent to administer any other investigational vaccine or agent from one month prior to enrollment through to the conclusion of the study;
• who received a dose of influenza treatment (commercial or investigational) one month prior to enrollment. The prophylactic use of influenza antivirals is not permitted.
• who receive any influenza vaccine in the 6 months prior to enrollment, or intend to receive a non-study influenza vaccine after enrollment;
• with any medical conditions that in the opinion of the investigator might interfere with interpretation of the study results; Note: A pregnant household member is not considered a contraindication to enrollment.