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Medical Areas: Immunology | Infections and Infectious Diseases | Vaccines
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FluMist ( Influenza Virus Vaccine)
The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Approval Status: Approved June 2003
Treatment Area: Influenza
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
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.
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%.
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
Adverse events associated with the use of Boniva may include
(but are not limited to) the following:
- Runny Nose
- Sore Throat
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
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.
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;
Sullivan KM. Health impact of influenza in the
United States. Pharmacoeconomics. 1996;9 Suppl.