Current Status of Live Attenuated Influenza Vaccine in the United States for Seasonal and Pandemic Influenza

Christopher S. Ambrose; Catherine Luke; Kathleen Coelingh

Disclosures

Influenza Resp Viruses. 2008;2(6):193-202. 

In This Article

Mechanism of Action and Efficacy in Children

Mechanism of Action

Live attenuated influenza vaccine viruses replicate primarily in the ciliated epithelial cells of the nasopharyngeal mucosa to induce immune responses (via mucosal immunoglobulin [Ig]A, serum IgG antibodies, and cellular immunity), but LAIV viruses do not replicate well at the warmer temperatures found in the lower airways and lung.[7,10] During the course of replication, all LAIV viral proteins would be presented to the immune system in their native conformation and in the context of histocompatibility proteins; resultant immune responses should mimic those of natural infection with influenza virus.

Efficacy in Children

LAIV Efficacy Relative to Placebo. The efficacy of LAIV relative to placebo has been examined in six studies in children aged 6–71 months ( Table 2 ); LAIV is currently approved for use in children 24 months and older. Following first-year vaccination, efficacy against illness caused by antigenically matched strains (A/H1N1, A/H3N2, and B) has ranged from 62·2% to 93·4%. In studies that assessed efficacy in a second season following revaccination, efficacy ranged from 73·6% to 100%. LAIV has also been shown to reduce the incidence of all-cause febrile otitis media by 30–32% and influenza-associated otitis media by 73–98% compared with placebo.[11,12,13]

In addition to high levels of efficacy against matched strains, LAIV has shown protection against antigenically mismatched strains. In year 2 of study AV006, LAIV demonstrated 86% protection against the drifted variant A/Sydney/5/97 (H3N2) strain.[14] Additionally, when an influenza B variant circulated in 2000–2001, a single dose of LAIV in children 1·5–18 years of age was estimated to provide 66% (95% CI: 9, 87) protection in a large, nonrandomized, open-label study (n = 2281).[15,16] During the 2003–2004 season, LAIV was estimated to have provided 56% (95% CI: 24, 84) efficacy against the mismatched A/Fujian/411/02 (H3N2) virus (n = 1706).[17]

Although two doses of influenza vaccine are recommended in previously unvaccinated young children, three studies[11,13,18] compared one dose of LAIV with placebo in this population. Efficacy of a single dose was 58% (95% CI: 45, 68), 60% (95% CI: 31, 77), and 89% (95% CI: 65, 96), respectively. Greater efficacy is provided by two doses, and thus two doses are recommended. However, given that compliance with the two-dose regimen is low,[19] it is reassuring that a single dose of LAIV has provided clinically significant protection for vaccine-naive young children who fail to receive a second dose.

With regard to duration of protection, in one placebo-controlled study LAIV demonstrated protection during a season in which influenza circulated for up to 13 months following vaccination.[17] Additionally, two placebo-controlled studies demonstrated that two doses of LAIV in year 1 provided 56% (95% CI: 31, 73) and 57% (95% CI: 6, 82) protection through a second influenza season without revaccination.[13,18]

LAIV Efficacy Relative to Inactivated Vaccine. Three studies have compared the efficacy of trivalent inactivated influenza vaccine (TIV) and LAIV in children aged 6–59 months, 6–71 months with a history of recurrent respiratory tract infections, and 6–17 years with stable, medically-treated asthma ( Table 3 ). In these studies, LAIV was more effective than TIV, reducing culture-confirmed influenza illness caused by matched strains by 35–53%.[20,21,22] Across the studies, significant reductions were seen against antigenically matched A/H1N1 and B strains as well as antigenically mismatched A/H3N2 strains. LAIV also reduced influenza-associated otitis media by 51% when compared with TIV in Study MI-CP111.[22] Due to insufficient data, the current US prescribing information states that LAIV should not be administered to any individuals with asthma or children < 5 years of age with recurrent wheezing because of the potential for increased risk of wheezing post-vaccination unless the potential benefit outweighs the potential risk.[23]

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