Efficacy of the New Intranasal Live Attenuated Influenza Vaccine for the 2018-2019 Season

George Cullina, Pharm.D, Cashwise Clinic Pharmacy / ACMC

Background: The intranasal live attenuated influenza vaccine (LAIV) was approved in 2003 and remained part of the Center for Disease Control’s (CDC) Advisory Committee on Immunization Practices (ACIP) until its removal before the 2016-2017 flu season. This intranasal option was used primarily in patients aged between 2-49 years old who preferred to avoid intramuscular injections. After several years of being outside of the recommendations, the CDC’s ACIP reviewed the new formulation of the intranasal LAIV for the 2018-2019 flu season.

Evidence: The intranasal LAIV was officially removed from recommendation before the 2016-2017 season following several years of reduced efficacy in what was speculated to be the H1N1 strain. Influenza vaccines include two  influenza A viruses (H1N1 and H3N2) and one or two influenza B viruses for trivalent or quadrivalent vaccines, respectively.

The study Vaccine failure and serologic response to live attenuated and inactivated influenza vaccines in children during the 2013–2014 season examined this issue. Hemagglutination inhibition (HI) assays were used against vaccine reference strains before and after vaccine administration to test for seroconversion. Seroconversion was used as a surrogate marker to assess for protection against the H1N1 strain. Baseline H1N1 geometric mean titers (GMTs), a marker used to measure effective serologic responses, were similar at baseline between the inactive influenza vaccine (IIV) and LAIV. However, after vaccination they discovered 40% of IIV patients experienced seroconversion as compared with only 2% of LAIV patients.

The efficacy of this intermediate marker was demonstrated when three (3%) IIV recipients and eight (13%) LAIV recipients (P=0.02) tested positive for H1N1 on swabs. After completing an age-adjusted, multivariable logistic regression, LAIV was the only factor associated associated with vaccine failure against H1N1. This gap in efficacy in protecting against the H1N1 strain led to the vaccine’s loss in favor by the CDC in 2016.

The CDC states that the new LAIV, which includes A/Slovenia/2903/2015, has much higher seroconversion rates than the previous vaccine, which had A/Bolivia/559/2013. The increased seroconversion is believed to be produced by an improved replicative fitness. This means that the new strain has a higher capacity and greater adaptability to be replicated, and therefore produce a seroconversion.

Discussion: Based on the new formulation for the LAIV, the CDC’s ACIP includes the new intranasal LAIV in its recommended 2018-2019 influenza vaccine options. While the new LAIV has much higher seroconversion rates, there are unfortunately no efficacy studies on the new LAIV for preventing influenza in a patient population. The American Academy of Pediatrics (AAP) convened to discuss the updated ACIP recommendation and is officially giving preference to IIV over LAIV, stating that the nasal vaccine may not offer full protection against influenza. Their rationale is that the LAIV’s efficacy was inferior to IIV against H1N1 during past seasons and is currently unknown for H1N1 for this upcoming season.

Clinical Impact: It is important to note that while seroconversion has been proven, the effectiveness of the updated LAIV against currently circulating H1N1 viruses is not yet known. Due to this lack of efficacy against the currently circulating H1N1 viruses, the AAP recommends using the IIV intramuscular vaccine instead of the LAIV intranasal vaccine. Based on the evidence available, it is reasonable to use the intranasal LAIV in patients who would otherwise not receive a flu vaccine.

References:

  1. Shelton, Chasity M., et al. “To Mist or Not to Mist: An Update on the Recommendations for Live-Attenuated Influenza Vaccine.” Journal of the American Pharmacists Association, vol. 58, no. 4, 2018, pp. 457–459., doi:10.1016/j.japh.2018.06.005.

  2. “Influenza (Flu).” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 14 Dec. 2017, www.cdc.gov/flu/protect/vaccine/quadrivalent.htm.

  3. King, Jennifer P., et al. “Vaccine Failure and Serologic Response to Live Attenuated and Inactivated Influenza Vaccines in Children during the 2013–2014 Season.” Vaccine, vol. 36, no. 9, 2018, pp. 1214–1219., doi:10.1016/j.vaccine.2018.01.016.

  4. “Morbidity and Mortality Weekly Report (MMWR).” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 7 June 2018, www.cdc.gov/mmwr/volumes/67/wr/mm6722a5.htm.

   5. Munoz-Rivas, Flor M., and Henry H. Bernstein. “AAP Influenza Immunization Recommendations Revised for 2018-'19 Season.” AAP Gateway, American Academy of Pediatrics, 15 Aug. 2018, www.aappublications.org/news/2018/06/07/influenza060718.