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General Information

FluMist (Influenza Virus Vaccine Live) Intranasal is a live trivalent nasally administered vaccine intended for active immunization for the prevention of influenza. The vaccine contains live attenuated influenza viruses that replicate in the nasopharynx of the recipient and are shed in respiratory secretions.

Each 0.5 mL dose is formulated to contain live attenuated influenza virus of the strains: A/New Caledonia/20/99 (H1N1), A/Panama/2007/99 (H3N2) (A/Moscow/10/99-like), and B/Hong Kong/330/2001.

The vaccine is indicated for active immunization for the prevention of disease caused by influenza A and B viruses in healthy children and adolescents, 5-17 years of age, and healthy adults, 18-49 years of age. It is not indicated for children less than 5 years of age, or adults 50 years of age and older.

Clinical Results

Pediatric Study
FDA pediatric approval was based on a multi-center, randomized, double-blind, placebo-controlled trial enrolling over 4719 healthy children and was designed to evaluate the efficacy of FluMist against culture confirmed influenza over two successive seasons. The primary endpoint for the first year of the trial was the prevention of culture-confirmed influenza illness due to antigenically matched wild-type influenza in healthy children who received two doses of vaccine.

Results showed that subject’s 60-71 months of age who received two doses of vaccine compared with placebo experienced a significant reduction in the incidence of culture-confirmed influenza. Additionally, children who received one doses of vaccine compared to one dose of placebo experienced a significant reduction in the incidence of culture-confirmed influenza. Roughly, 85% of subject in the first year returned for the second year of the Pediatric Efficacy Study, including a subset of 544 children 60-84 months of age.

During the second year of the trial, children remained in the same treatment group as in year one and received a single dose of FluMist or placebo. The primary endpoint of the trial was the prevention of culture-confirmed influenza illness due to antigenically matched wild-type influenza after a single annual revaccination dose of FluMist. In the subset of 544 children 60-84 months of age, illness associated with culture-confirmed illness in the second year was similar in scope and severity to that in the first year. The overall efficacy of FluMist against culture-confirmed wild-type influenza, regardless of antigenic match, was 86.9%.

Adult Study
FDA adult approval was based on a multi-center, randomized, double blind, placebo-controlled trial enrolling 3920 healthy adults 18-49 years of age. The trial was designed to evaluate the effectiveness of FluMist in the reduction of influenza-like illness during the peak influenza outbreak period at each site, based on community surveillance. The efficacy against culture confirmed influenza was not assessed. The primary endpoint of the trial was the reduction in the proportion of participants with one or more episodes of any febrile illness (AFI). Adults had AFI if they had symptoms for at least two days with fever on at least one day and if they had two or more symptoms (fever, chills, headache, runny nose, sore throat, cough, muscle aches, tiredness/weakness) on at least one day. Two other influenza-like illness definitions were also assessed: severe febrile illness (SFI), and febrile upper respiratory illness (FURI). SFI was defined as having at least three consecutive days of symptoms, at least one day of fever, and two or more symptoms on at least three days. FURI was defined as at least two consecutive days of upper respiratory infection (URI) symptoms (runny nose, sore throat, or cough), fever on at least one day, and at least two URI symptoms on at least one day. Results showed that during the outbreak period, FluMist subject did not experience a significant reduction in AFI; however, significant reductions were observed for SFI and FURI.

The efficacy in adults was also demonstrated in a vaccine challenge study. The multi-center, randomized, double-blind, placebo-controlled study enrolled healthy adults 18-41 years of age who were serosusceptible to at least one strain included in the vaccine. Adults were randomized to receive FluMist or placebo. Laboratory-documented influenza illness due to all three strains combined was reduced compared to placebo by 85% in FluMist recipients.

Side Effects

Adverse events associated with the use of Boniva may include (but are not limited to) the following:

Cough
Runny Nose
Sore Throat
Fever
Headache
Chills
Congestion

Mechanism of Action

The exact mechanisms of protection against influenza following treatment with FluMist vaccine are not fully understood. Serum antibodies, mucosal antibodies and influenza-specific T cells may play a role in prevention and recovery from infection. Vaccination with FluMist has been demonstrated to induce influenza strain-specific serum antibodies. The cumulative effect of antigenic properties and the included phenotypes is that the vaccine viruses replicate in the nasopharynx to produce protective immunity.

Each of the three influenza virus strains contained in FluMist is a genetic reassortant of a Master Donor Virus (MDV) and a wild-type influenza virus. The MDVs (A/Ann Arbor/6/60 and B/Ann Arbor/1/66) were developed by serial passage at sequentially lower temperatures in specific pathogen-free (SPF) primary chick kidney cells. During this process, the MDVs acquired the ca, ts and att phenotype and multiple mutations in the gene segments that encode viral proteins other than the surface glycoproteins. The individual contribution of the genetic sequences of the six non-glycoprotein MDV genes (“internal gene segments”) to the ca, ts, and att phenotype is not completely understood. However, at least five genetic loci in three different internal gene segments of the Type A MDV and at least three genetic loci in two different internal gene segments of the Type B MDV contribute to the ts property.

Literature References

Centers for Disease Control and Prevention. Prevention and control of Influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2003; 52 (No.RR-8): 1-34.

Jin H, et al. Multiple amino acid residues confer temperature sensitivity to human influenza virus vaccine strains (FluMist) derived from cold-adapted A/Ann Arbor/6/60. Virology. 2003; 306:18-24.

Monto AS, Sullivan KM. Acute respiratory illness in the community. Frequency of illness and the agents involved. Epidemiol Infect. 1993;110:145-160.

Murphy BR, Coelingh KC. Principles underlying the development and use of live attenuated cold-adapted influenza A and influenza B virus vaccines. Viral Immunol. 2002; 15:295-323.

Sullivan KM. Health impact of influenza in the United States. Pharmacoeconomics. 1996;9 Suppl. 3:26-33.