, Volume 71, Issue 12, pp 1591-1622
Date: 24 Sep 2012

Live Attenuated Influenza Vaccine (FluMist®; Fluenz™)

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Live attenuated influenza vaccine (LAIV) is an intranasally administered trivalent, seasonal influenza vaccine that contains three live influenza viruses (two type A [H1N1 and H3N2 subtypes] and one type B).

LAIV was effective in protecting against culture-confirmed influenza caused by antigenically matched and/or distinct viral strains in children aged ≤71 months enrolled in three phase III trials. LAIV was superior to trivalent inactivated influenza vaccine (TIV) in protecting against influenza caused by antigenically-matching viral strains in a multinational phase III trial in children aged 6–59 months. LAIV was also significantly more effective than TIV in decreasing the incidence of culture-confirmed influenza illness in two open-label studies (in children with recurrent respiratory tract illnesses aged 6–71 months and in children and adolescents with asthma aged 6–17 years).

LAIV did not differ significantly from placebo in preventing febrile illnesses in adults (primary endpoint) enrolled in a phase III trial. However, LAIV significantly reduced the incidence of febrile upper respiratory tract illnesses (URTI), severe febrile illnesses, febrile URTI-related work absenteeism and healthcare provider use. In another well designed trial in adults, LAIV significantly reduced the incidence of symptomatic, laboratory-confirmed influenza compared with placebo (but not intramuscular TIV).

LAIV was generally well tolerated in most age groups, with the majority of adverse events being mild to moderate in severity, and runny nose/nasal congestion being the most common. In a large phase III trial, LAIV, compared with TIV, was associated with an increased incidence of medically significant wheezing in vaccine-naive children aged <24 months and an increased incidence of hospitalization in children aged 6–11 months; LAIV is not approved for use in children <24 months.

LAIV was not always associated with high rates of seroconversion/seroresponse, particularly in older children and adults, or in subjects with detectable levels of haemagglutination-inhibiting antibodies at baseline. However, LAIV did elicit mucosal (nasal) IgA antibody responses and strong cell-mediated immunity responses. Only one confirmed case of LAIV virus transmission to a placebo recipient (who did not become ill) occurred in a transmission study conducted in young children. The immunogenic response to LAIV in young healthy children was not affected by concomitant administration with other commonly administered childhood vaccines.

In conclusion, intranasal LAIV seasonal influenza vaccine is effective and well tolerated in children, adolescents and adults. LAIV was more effective than TIV in children, although this advantage was not seen in adults. In the US, LAIV is indicated for the active immunization of healthy subjects aged 2–49 years against influenza disease caused by virus subtypes A and type B contained in the vaccine.

Various sections of the manuscript reviewed by: S. Ashkenazi, Schneider Children’s Medical Center, Petah-Tikva, Israel; D.M. Fleming, Research and Surveillance Centre, The Royal College of General Practitioners, Birmingham, United Kingdom; R. Samakoses, Infectious Disease Unit, Phramongkutklao Hospital, Bangkok, Thailand; T. Vesikari, Department of Virology/Vaccine Research, University of Tampere Medical School, Tampere, Finland.

Data Selection

Sources: Medical literature (including published and unpublished data) on ‘intranasal live attenuated influenza vaccine’ was identified by searching databases since 1996 (including MEDLINE, EMBASE and inhouse AdisBase), bibliographies from published literature, clinical trial registries/databases and websites (including those of regional regulatory agencies and the manufacturer). Additional information (including contributory unpublished data) was also requested from the company developing the drug.
Search strategy: MEDLINE, EMBASE and AdisBase search terms were ‘live attenuated intranasal vaccine’ or ‘intranasal live attenuated influenza vaccine’ or (‘live’ and ‘attenuated’ and ‘intranasal’ and ‘vaccine’ and ‘cold-adapted’). Searches were last updated 16 August 2011.
Selection: Studies in children or adults who received intranasal live attenuated influenza vaccine. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.
Index terms: intranasal live attenuated influenza vaccine, protective efficacy, reactogenicity, tolerability, immunogenicity.