On Jun. 8, 2018, the U.S. Centers for Disease Control and Prevention (CDC) published Immunization Practices Advisory Committee (ACIP)’s recommendations for the use of quadrivalent live attenuated influenza vaccine (LAIV4) in the 2018-19 influenza season. Quadrivalent live attenuated influenza vaccine (LAIV4) (FluMist Quadrivalent, MedImmune) has been licensed in the United States since 2012 and was first available during the 2013–14 influenza season, replacing LAIV3.

During the 2016–17 and 2017–18 influenza seasons, the Advisory Committee on Immunization Practices (ACIP) recommended that LAIV4 not be used because of concerns about low effectiveness against influenza A(H1N1)pdm09-like viruses circulating in the United States during the 2013–14 and 2015–16 seasons. On February 21, 2018, ACIP recommended that LAIV4 be an option for influenza vaccination of persons for whom it is appropriate for the 2018–19 season. This document provides an overview of the information discussed in the decision-making process leading to this recommendation. A description of methodology and data reviewed will be included in the background materials that will supplement the 2018–19 ACIP Influenza Recommendations, which will replace the 2017–18 ACIP influenza statement, and which will also contain guidance for the use of LAIV4.

Before the 2009 influenza A(H1N1) pandemic, three randomized trials noted superior relative efficacy of LAIV3 compared with trivalent inactivated influenza vaccine (IIV3) among children. However, LAIV4 demonstrated no statistically significant effectiveness against influenza A(H1N1)pdm09-like viruses among children aged 2 through 17 years in U.S. studies conducted during the 2013–14 and 2015–16 seasons, during which these viruses predominated. This lack of effectiveness was postulated as attributable to decreased replicative fitness of the influenza A(H1N1)pdm09-like viruses included in LAIV4 during those seasons (A/California/7/2009 for 2013–14 and A/Bolivia/559/2013 for 2015–16). Investigations into the potential cause of this reduced effectiveness against influenza A(H1N1)pdm09 revealed that these LAIV viruses exhibited reduced replication in human nasal epithelial cells, compared with prepandemic influenza A(H1N1) LAIV viruses. For the 2017–18 season, a new influenza A(H1N1)pdm09-like virus (A/Slovenia/2903/2015) was included in LAIV4, replacing A/Bolivia/559/2013. However, LAIV4 was not recommended for use in the United States during 2017–18, and no U.S. effectiveness estimates were available.

Review of LAIV effectiveness data for previous seasons in the United States confirms low to no significant effectiveness of LAIV against influenza A(H1N1)pdm09-like viruses. However, LAIV was generally effective against influenza B viruses and was of similar effectiveness to IIV against influenza A(H3N2) viruses. No effectiveness estimates were available for the current formulation of LAIV4 containing A/Slovenia/2903/2015 against influenza A(H1N1)pdm09-like viruses at the time of the review

Data presented by the manufacturer indicated that the new LAIV4 influenza A(H1N1)pdm09-like virus, A/Slovenia/2903/2015, was shed by a higher proportion of children during days 4 through 7 following the first of 2 doses of vaccine. A/Slovenia/2903/2015 induced significantly higher antibody responses than its predecessor, A/Bolivia/559/2013. Seroconversion rates to A/Slovenia/2903/2015 were comparable to those obtained in response to prepandemic influenza A(H1N1) LAIV strains used during seasons in which the vaccine was observed to be effective against A(H1N1) influenza viruses.

For the 2018–19 U.S. influenza season, providers may choose to administer any licensed, age-appropriate influenza vaccine (IIV, recombinant influenza vaccine [RIV], or LAIV4). LAIV4 is an option for those for whom it is otherwise appropriate. No preference is expressed for any influenza vaccine product. ACIP will continue to review data concerning the effectiveness of LAIV4 as they become available. Providers should be aware that the effectiveness of the updated LAIV4 containing A/Slovenia/2903/2015 against currently circulating influenza A(H1N1)pdm09-like viruses is not yet known.