Live, attenuated influenza virus vaccine is a new option for controlling influenza. Nichol and colleagues conducted a randomized, double-blind controlled trial to determine the safety and effectiveness of this intranasally administered vaccine when used in healthy adults. Patients were recruited to participate if they were 18 to 64 years of age, worked outside the home at least 30 hours per week, had health insurance and were able to participate in follow-up telephone calls. Patients were excluded from the study if they were allergic to eggs or egg products, were pregnant (or possibly pregnant), had already received an influenza vaccination for the year or had a febrile respiratory illness within the past three days. Live, attenuated influenza virus vaccine and placebo were administered as an intranasal spray in a single dose between mid-September and mid-November. Vaccine and placebo were administered by the participant or by a study staff member.
Participants filled out a reactogenicity symptom card and kept a daily record of temperature and respiratory and systemic symptoms. Participants also recorded whether they had missed work or taken antibiotics or over-the-counter medications after the vaccination. One week after the vaccination or placebo, patients were called and reminded to return the cards. One month after the vaccination, subjects were interviewed about other events that may have occurred during the past month. The primary end point was a febrile illness (fever on at least one day plus symptoms for at least two consecutive days). Other categories of illness were severe febrile illness and febrile upper respiratory tract illness.
There were 3,041 patients who received live, attenuated influenza virus vaccine and 1,520 who received placebo. About 70 percent in each group self-administered the nasal spray, and 96 percent of these patients did so without difficulty. Patients who received live, attenuated influenza virus vaccine were more likely to have a runny nose or a sore throat in the week following the vaccination. Neither of these symptoms made participants more likely to use antibiotics or over-the-counter medications. None of the adverse events occurring in the 28 days after the vaccine or placebo administration were considered related to the treatment. Of the febrile illnesses experienced by the vaccine recipients, 73 percent were considered severe febrile illnesses, and 61 percent were febrile upper respiratory tract illnesses. In the placebo group, these figures were 81 and 72 percent, respectively. The total number of febrile illnesses was similar in the two groups, but all illness outcomes (such as health care visits and missed work days) were reduced in the vaccine group. The authors conclude that live, attenuated intranasally administered influenza vaccine is safe and effective in healthy adults.