In the JournalsPerspective

AAP, ACIP’s previous FluMist recommendations supported by 2013-2016 data

Concerns about the effectiveness of the quadivalent, live-attenuated influenza vaccine, or LAIV4, prompted both the AAP and the Advisory Committee on Immunization Practices to recommend against its use during the 2016-2017 and 2017-2018 influenza seasons. New findings published in Pediatrics appear to support those recommendations.

In February 2018, the ACIP once again recommended LAIV4 — marketed as FluMist (AstraZeneca) — for use in patients aged 2 to 49 years after the manufacturer modified the vaccine and presented evidence that it protected more effectively against influenza A(H1N1)pdm09. The AAP, however, continues to advise against the use of LAIV4 but suggests it could be used in children who would not otherwise be vaccinated. The vaccine is administered intranasally, making it a more attractive option for parents and pediatric patients than an injection.

Jessie R. Chung, MPH, an epidemiologist in the CDC’s Influenza Division, and colleagues analyzed pooled data from five studies conducted between the 2013-2014 and 2015-2016 influenza seasons. These studies examined the efficacy of LAIV4 and inactivated influenza vaccine (IIV) in children and adolescents aged 2 to 17 years.

The researchers identified 17,173 pediatric and adolescent patients with influenza during the study period. Of these patients, 4,579 were administered IIV and 1,979 were administered LAIV4.

 
Click to enlarge

According to Chung and colleagues, vaccine effectiveness against A(H1N1)pdm09 was 67% (95% CI, 62%-72%) for IIV and only 20% (95% CI, –6% to 39%) for LAIV4. Children who received LAIV4 were more than two times as likely to be infected with influenza A(H1N1)pdm09 compared with children who received IIV (OR = 2.66; 95% CI, 2.06-3.44).

Additional efforts have been taken by the manufacturer to identify the cause of the reduced effectiveness of influenza A/H1N1pdm09 LAIV strains,” Chung and colleagues wrote. “The LAIV H1N1 vaccine virus for the 2017-2018 and 2018-2019 influenza seasons — A/Slovenia/2309/2015 — has demonstrated improved replicative fitness in the laboratory and increased shedding and serum antibody responses among children compared with A/Bolivia/559/2013” — the strain that was previously used in the vaccine. – by Katherine Bortz

Disclosures: Chung reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

Concerns about the effectiveness of the quadivalent, live-attenuated influenza vaccine, or LAIV4, prompted both the AAP and the Advisory Committee on Immunization Practices to recommend against its use during the 2016-2017 and 2017-2018 influenza seasons. New findings published in Pediatrics appear to support those recommendations.

In February 2018, the ACIP once again recommended LAIV4 — marketed as FluMist (AstraZeneca) — for use in patients aged 2 to 49 years after the manufacturer modified the vaccine and presented evidence that it protected more effectively against influenza A(H1N1)pdm09. The AAP, however, continues to advise against the use of LAIV4 but suggests it could be used in children who would not otherwise be vaccinated. The vaccine is administered intranasally, making it a more attractive option for parents and pediatric patients than an injection.

Jessie R. Chung, MPH, an epidemiologist in the CDC’s Influenza Division, and colleagues analyzed pooled data from five studies conducted between the 2013-2014 and 2015-2016 influenza seasons. These studies examined the efficacy of LAIV4 and inactivated influenza vaccine (IIV) in children and adolescents aged 2 to 17 years.

The researchers identified 17,173 pediatric and adolescent patients with influenza during the study period. Of these patients, 4,579 were administered IIV and 1,979 were administered LAIV4.

 
Click to enlarge

According to Chung and colleagues, vaccine effectiveness against A(H1N1)pdm09 was 67% (95% CI, 62%-72%) for IIV and only 20% (95% CI, –6% to 39%) for LAIV4. Children who received LAIV4 were more than two times as likely to be infected with influenza A(H1N1)pdm09 compared with children who received IIV (OR = 2.66; 95% CI, 2.06-3.44).

Additional efforts have been taken by the manufacturer to identify the cause of the reduced effectiveness of influenza A/H1N1pdm09 LAIV strains,” Chung and colleagues wrote. “The LAIV H1N1 vaccine virus for the 2017-2018 and 2018-2019 influenza seasons — A/Slovenia/2309/2015 — has demonstrated improved replicative fitness in the laboratory and increased shedding and serum antibody responses among children compared with A/Bolivia/559/2013” — the strain that was previously used in the vaccine. – by Katherine Bortz

Disclosures: Chung reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

    Perspective
    José R. Romero

    José R. Romero

    During the June 2016 meeting of the ACIP, the committee reviewed preliminary VE data of LAIV collected from the U.S. Influenza Vaccine Effectiveness Network during the 2015-2016 influenza season for children aged 2 to 17 years. Those data demonstrated low efficacy against any influenza virus during that season (VE = 3%; 95% CI, –49% to 37%).

    In comparison, the VE for IIV was 63% (95% CI, 52%-72%). The conclusion that LAIV did not work as well as IIV was also supported by additional non-CDC studies. Further, lower-than-expected VE for LAIV was also observed in the 2013-2014 and 2014-2015 seasons. Based on the data above, the ACIP recommended that LAIV not be used during the 2016-2017 influenza season. That recommendation was continued for the 2017-2018 season.  

    In their report, Chung and colleagues presented findings of an analysis of pooled individual patient-level data VE for LAIV and IIV obtained from the CDC’s U.S. Influenza Vaccine Effectiveness Network and four other sources for influenza seasons 2013-2014, 2014-2015 and 2015-2016. Their findings support the preliminary VE data presented to the ACIP in 2016, showing a reduced VE of LAIV against influenza A(H1N1)pdm09. LAIV demonstrated a possible benefit over IIV against influenza B viruses. However, the finding did not reach statistical significance. The authors also showed that previous season influenza immunization with IIV or LAIV did not explain the lower VE for current season LAIV.

    In February 2018, the ACIP reviewed pooled VE data from five U.S. observational studies for children aged 2 to 17 years receiving LAIV and IIV during influenza seasons 2013-2014 through 2015-2016, published literature on the VE of LAIV among children during the 2010-2011 through 2016-2017 influenza seasons, and information submitted by the manufacturer of LAIV on the viral shedding and the immunogenicity of LAIV containing a new influenza A(H1N1)pdm09-like virus (A/Slovenia/2903/2015) in U.S. children aged 24 months to younger than 4 years. The latter documented improved replicative fitness in the lab, increased viral shedding in vaccine recipients and increased serum antibody responses compared with the A/Boliva/559/2013 stain. Based on its analysis of the information presented, the ACIP recommended that providers could choose to administer any licensed, age-appropriate influenza vaccine — IIV or LAIV — for children and adolescents as appropriate. No preference is expressed for any influenza vaccine product by the ACIP.

    As indicated in their article, preliminary data from the United Kingdom suggest that the VE of LAIV containing the A/Slovenia/2903/2015 influenza strain was favorable.  Future information on the VE of LAIV from the U.S. and other countries will help greatly to address remaining questions regarding this vaccine.

    • José R. Romero, MD, FAAP, FIDSA, FPIDS
    • Chair of the ACIP
      Section chief of pediatric infectious diseases,
      University of Arkansas for Medical Sciences
      Infectious Diseases in Children Editorial Board member