The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices has voted to scrap the use of the live attenuated influenza vaccine for the 2016-2017 flu season.
ACIP’s interim recommendation guidance to the CDC is that “no live attenuated influenza vaccines (LAIV) should be used in any setting,” after reviewing data showing that for three consecutive influenza seasons, LAIV’s vaccine effectiveness (VE) against any flu virus was 3% (95% confidence interval, -49%-37%) in children aged 2-17 years. Meanwhile, injectable inactivated influenza vaccine (IIV) had a VE estimate of 63% (95% CI, 52%-72%) against any flu virus in that age group. Findings were similar across age groups.
Louise A. Koenig/Frontline Medical News
CDC epidemiologist Brendan Flannery, Ph.D., painted a damning picture of the intranasal LAIV, presenting preliminary data from the U.S. Flu Vaccine Effectiveness Network for 2015-2016 that showed quadrivalent LAIV offered children “no significant protection against influenza A(H1N1)pdm09.” He also presented 2015-2016 national cohort data from Finland showing that unadjusted vaccine effectiveness (VE) against the H1N1 strain for LAIV in 2-year-olds was 47%, compared with 78% for IIV. Dr. Flannery also cited a series of other U.S. and international studies that did not support the use of LAIV, including unpublished Department of Defense 2015-2016 influenza season data for military families indicating that VE for LAIV against the strain last season was “insignificant” in children aged 2-17 years.
Data from an industry study of the quadrivalent LAIV FluMist (MedImmune) also indicated that in this cohort, for the 2015-2016 influenza season, LAIV underperformed compared with IIV, 46% vs. 65%.
Still more bad news for LAIV came from an English study published online just as the ACIP meeting was getting underway. Those data showed that from October 2015 through May 2016, LAIV in children aged 2-17 years had a VE of 57.6% against influenza A and B.
Debate over whether to pull support for LAIV entirely or to allow the use of it in certain circumstances – such as when a person declined a flu shot – hinged on the projected upheaval pulling LAIV is likely to cause.
Concerns were raised around what would happen in the case of LAIV vaccine orders already placed, over whether pulling LAIV would mean a shortage of other vaccine alternatives, and how communicating contingencies might only confuse the public, but several committee members spoke forcefully in favor of what they said the data compelled them to do.
“The science simply shows that LAIV has not worked for the past 3 years, whereas IIV has,” American Academy of Pediatrics Infectious Disease Committee’s Red Book editor, and AAP liaison to ACIP, Dr. David Kimberlin said before the vote.
Restricting but not prohibiting LAIV also would have allowed for an easier transition back to LAIV if the vaccine were successfully reformulated, ACIP Influenza Work Group Chair Dr. Ruth Karron said while presenting potential policy recommendations.
During the debate over whether to pull or limit support for the inhaled vaccine, Dr. Karron reminded the committee that at the time the Food and Drug Administration approved LAIV, serum antibody responses to both the tri- and quadrivalent vaccine were modest, prompting the FDA to call for effectiveness studies. “So, my question to the FDA now is, ‘What are their plans?’ ”
“We’ve seen the studies, but we’ve not really reviewed all the data,” Dr. Wellington Sun, the FDA’s ACIP liaison responded. “I think we have to acknowledge that LAIV has offered advantages over IIV in the past. At this point, we’re not ready to undertake a program for changing the prescriber’s information. We want to continue to work with MedImmune to find out the root cause of this phenomenon.”
“We’ve increased our research into understanding the biology of the H1N1pdm09 LAIV strains so we can improve their effectiveness in future seasons,” Dr. Chris Ambrose, vice president of U.S. medical affairs for infectious disease at MedImmune’s parent company AstraZeneca, told the committee.
“I think this is a very sad day for the influenza vaccination program,” ACIP chair Dr. Nancy Bennett said before adjourning the meeting. “We all had great hopes. It’s not over. If you’ve seen 1 influenza year, you’ve seen 1 influenza year. We may be back here next year having a very different discussion.”
The CDC is not obligated to adopt ACIP recommendations, but typically does. The committee also accepted a resolution to update the Vaccines for Children program in accordance with the recommendation to deny support for LAIV this flu season.
Thirteen members of the committee voted in favor of the recommendation. Dr. Edward Belongia abstained citing a conflict of interest, and Ms. Cynthia Pelligrini voted no, citing “insufficient time to consider this information.” The ICICLE trial NCT01997450, was sponsored by MedImmune, a subsidiary of AstraZeneca where Dr. Ambrose is vice president of U.S. medical affairs for infectious disease.