From the Journals

LAIV4 was less effective for children than IIV against influenza A/H1N1pdm09

View on the News

Viral interference, inadequate handling may explain decline in LAIV4 vaccine efficacy

There are many explanations for the decline in effectiveness of the live attenuated influenza vaccine (LAIV4), but the data are complicated by conflicting information from studies outside the United States indicating “reasonable protection” against influenza A/H1N1pdm09, A/H3N2, and influenza B, compared with the inactivated influenza virus (IIV), Pedro A. Piedra, MD, wrote in an accompanying editorial.

In 2016, the World Health Organization met to discuss LAIV effectiveness and highlighted factors such as methodological study differences, inadequate vaccine handling at distribution centers, intrinsic virological differences of the A/H1N1pdm09 virus, and increased preexisting population immunity in the United States since 2010 as potential explanations. During the transition from LAIV3 to LAIV4 for the 2013-2014 influenza season, viral interference may have also occurred when the influenza B strain was introduced into the vaccine, he added.

According to the CDC’s Advisory Committee on Immunization Practices (ACIP), viral growth properties of A/H1N1pdm09 has improved in LAIV4, and viral shedding also has improved for children between 2 years and 4 years of age. Although effectiveness numbers were not available for the ACIP recommendation, an interim analysis from Public Health England for the 2017-2018 influenza season found a vaccine effectiveness of 90.3% (95% confidence interval, 16.4%-98.9%).

“This early result is encouraging and supports the reintroduction of LAIV4 in the United States as an option for the control of seasonal influenza,” he said. “It also highlights the need for annual influenza vaccine effectiveness estimates and the importance of the U.S. Influenza Vaccine Effectiveness Network in providing updated information for ACIP recommendations.”

Dr. Piedra is from the departments of molecular virology and microbiology and pediatrics, Baylor College of Medicine, Houston. He reports being a consultant for AstraZeneca, Sanofi Pasteur, GlaxoSmithKline, and Merck Sharp and Dohme, and he has received travel support to present at an influenza seminar supported by Seqirus. His comments are from an editorial accompanying the article by Chung and colleagues ( Pediatrics. 2019. doi: 10.1542/peds.2018- 3290 ).



The live attenuated influenza vaccine was less effective against the influenza A/H1N1pdm09 virus in children and adolescents across multiple influenza seasons between 2013 and 2016, compared with the inactivated influenza vaccine, according to research published in the journal Pediatrics.

A child receives H1N1 flu mist. Louise A. Koenig/MDedge News

Jessie R. Chung, MPH, from the influenza division at the Centers for Disease Control and Prevention in Atlanta, and her colleagues performed an analysis of five different studies where vaccine effectiveness (VE) was examined for quadrivalent live attenuated vaccine (LAIV4) and inactivated influenza vaccine (IIV) in children and adolescents aged 2-17 years from 42 states.

The analysis included data from the U.S. Influenza Vaccine Effectiveness Network (6,793 patients), a study from the Louisiana State University Health Sciences Center (3,822 patients), the Influenza Clinical Investigation for Children (3,521 patients), Department of Defense Global, Laboratory-based, Influenza Surveillance Program (1,935 patients), and the Influenza Incidence Surveillance Project (1,102 patients) between the periods of 2013-2014 and 2015-2016. The researchers sourced current and previous season vaccination history from electronic medical records and immunization registries.

Of patients who were vaccinated across all seasons, there was 67% effectiveness against influenza A/H1N1pdm09 (95% confidence interval, 62%-72%) for those who received the IIV and 20% (95% CI, −6%-39%) for LAIV4. Among patients who received the LAIV4 vaccination, there was a significantly higher likelihood of developing influenza A/H1N1pdm09 (odds ratio, 2.66; 95% CI, 2.06-3.44) compared with patients who received the IIV vaccination.

With regard to other strains, there was similar effectiveness against influenza A/H3N2 and influenza B with LAIV4 and IIV vaccinations.

“In contrast to findings of reduced LAIV4 effectiveness against influenza A/H1N1pdm09 viruses, our results suggest a possible but nonsignificant benefit of LAIV4 over IIV against influenza B viruses, which has been described previously,” the investigators wrote.

Limitations of the study included having data only one season prior to enrollment and little available demographic information beyond age, gender, and geographic location.

The Influenza Clinical Investigation for Children was funded by MedImmune, a member of the AstraZeneca Group. Two of the researchers are employees of AstraZeneca. The other authors reported having no conflicts of interest. The U.S. Influenza Vaccine Effectiveness Network was supported by the CDC through cooperative agreements with the University of Michigan, Kaiser Permanente Washington Health Research Institute, Marshfield Clinic Research Institute, University of Pittsburgh, and Baylor Scott & White Health. At the University of Pittsburgh, the project also was supported by the National Institutes of Health.

SOURCE: Chung JR et al. Pediatrics. 2018. doi: 10.1542/peds.2018-2094.

Next Article: