Considerations for the Use of Live Attenuated Influenza Vaccine and Inactivated Influenza Vaccine When Either is Available

Both LAIV and IIV have been demonstrated to be effective in children and adults. Among adults, most comparative studies have demonstrated that LAIV and IIV were of similar efficacy or that IIV was more efficacious (23). Several studies conducted before the 2009 H1N1 pandemic demonstrated superior efficacy of LAIV in children (24–26). A randomized controlled trial conducted during the 2004–05 season among 7,852 children aged 6 through 59 months demonstrated a 55% reduction in culture-confirmed influenza among children who received trivalent LAIV (LAIV3) compared with those who received trivalent IIV (IIV3). LAIV3 efficacy was higher than that of IIV3 against both antigenically drifted and well-matched influenza viruses (24). In a comparative study conducted during the 2002–03 season, LAIV3 provided 53% greater relative efficacy compared with IIV3 in children aged 6 through 71 months who had previously experienced recurrent respiratory tract infections (25).

In June 2014, following review of evidence on the relative efficacy of LAIV compared with IIV for healthy children, ACIP recommended that when immediately available, LAIV should be used for healthy children aged 2 through 8 years who have no contraindications or precautions. However, data from subsequent observational studies of LAIV and IIV vaccine effectiveness indicated that LAIV did not perform as well as expected based upon the observations in earlier randomized trials (27,28). Analysis of data from three observational studies of LAIV4 vaccine effectiveness for the 2013–14 season (the first season in which LAIV4 was available) revealed poor effectiveness of LAIV4 against influenza A(H1N1)pdm09 among children aged 2 through 17 years (27). During this season, H1N1pdm09 virus predominated for the first time since the 2009 pandemic. The reasons for the lack of effectiveness of LAIV4 against influenza A(H1N1)pdm09 are still under investigation. Moreover, although one large randomized trial observed superior relative efficacy of LAIV3 compared with IIV3 against antigenically drifted H3N2 influenza viruses during the 2004–05 season (24), interim analysis of observational data from the U.S. Influenza Vaccine Effectiveness (U.S. Flu VE) Network for the early 2014–15 season (in which antigenically drifted H3N2 viruses were predominant) indicated that neither LAIV4 nor IIV provided significant protection in children aged 2 through 17 years; LAIV did not offer greater protection than IIV for these viruses (28).

In the absence of data demonstrating consistent greater relative effectiveness of the current quadrivalent formulation of LAIV, preference for LAIV over IIV is no longer recommended. ACIP will continue to review the effectiveness of influenza vaccines in future seasons and update these recommendations if warranted.

For children and adults with chronic medical conditions conferring a higher risk for influenza complications, data on the relative safety and efficacy of LAIV and IIV are limited. In a study comparing LAIV3 and IIV3 among children aged 6 through 17 years with asthma conducted during the 2002–03 season, LAIV conferred 32% increased protection relative to IIV in preventing culture-confirmed influenza; no significant difference in asthma exacerbation events was noted (26). Available data are insufficient to determine the level of severity of asthma for which administration of LAIV would be appropriate.

For 2015–16, ACIP recommends the following:

1. All persons aged ≥6 months should receive influenza vaccine annually. Influenza vaccination should not be delayed to procure a specific vaccine preparation if an appropriate one is already available.
2. For healthy children aged 2 through 8 years who have no contraindications or precautions, either LAIV or IIV is an appropriate option. No preference is expressed for LAIV or IIV for any person aged 2 through 49 years for whom either vaccine is appropriate. An age-appropriate formulation of vaccine should be used.
3. LAIV should not be used in the following populations:
   • Persons aged <2 years or >49 years;
   • Persons with contraindications listed in the package insert:
     • Children aged 2 through 17 years who are receiving aspirin or aspirin-containing products;
     • Persons who have experienced severe allergic reactions to the vaccine or any of its components, or to a previous dose of any influenza vaccine;
   • Pregnant women;
   • Immunocompromised persons (see also “Vaccine Selection and Timing of Vaccination for Immunocompromised Persons”);
   • Persons with a history of egg allergy;
   • Children aged 2 through 4 years who have asthma or who have had a wheezing episode noted in the medical record within the past 12 months, or for whom parents report that a health care provider stated that they had wheezing or asthma within the last 12 months (Table, footnote). For persons aged ≥5 years with asthma, recommendations are described in item 4 of this list;
   • Persons who have taken influenza antiviral medications within the previous 48 hours.
4. In addition to the groups for whom LAIV is not recommended above, the “Warnings and Precautions” section of the LAIV package insert indicates that persons of any age with asthma might be at increased risk for wheezing after administration of LAIV (29). The package insert also notes that the safety of LAIV in persons with other underlying medical conditions that might predispose them to complications after wild-type influenza virus infection (e.g., chronic pulmonary, cardiovascular [except isolated hypertension], renal, hepatic, neurologic, hematologic, or metabolic disorders [including diabetes mellitus]) (2), has not been established. These conditions, in addition to asthma in persons aged ≥5 years, should be considered precautions for the use of LAIV.
5. Persons who care for severely immunosuppressed persons who require a protective environment should not receive LAIV, or should avoid contact with such persons for 7 days after receipt, given the theoretical risk for transmission of the live attenuated vaccine virus to close contacts.