LAIV, Inactivated Flu Vaccine Offer Similar Protection

Lara C. Pullen, PhD

August 16, 2016

The intranasal trivalent live attenuated influenza vaccine (LAIV) and the trivalent inactivated influenza vaccine (IIV) provide similar protection for communities, according to results of a cluster randomized blinded trial.

Mark Loeb, MD, from McMaster University in Hamilton, Ontario, Canada, and colleagues published their findings online August 16 in the Annals of Internal Medicine. The study, which was conducted between October 2012 and May 2015, was designed to determine whether immunizing children and adolescents with LAIV provides better community protection than immunizing with IIV.

The investigators randomly assigned children to receive either LAIV or IIV by community (52 Hutterite communities participated). The primary outcome was a non-inferiority comparison of influenza rates between LAIV and IIV groups, including immunized Hutterite children (n = 1186), aged 36 months to 15 years, and 3425 community members who were not immunized. Of the children in the study, 80% were aged 6 years or older.

During the 3 year study, the mean vaccine coverage among eligible children in the LAIV group was 76.7%, and 72.4% in the IIV group.

The investigators performed intense active influenza surveillance and found that both LAIV and IIV had a similar effect on laboratory-confirmed influenza A and B viruses. Specifically, the rate of influenza virus infection was 5.3% in the LAIV group compared with 5.2% in the IIV group.

"Our results suggest that vaccinating children with LAIV does not confer better community protection against influenza than IIV," the authors write in their discussion. "Although the choice of an influenza vaccine for children may depend on various factors, our data suggest no additional benefit of LAIV over IIV."

Centers for Disease Control and Prevention Has Recommended Against LAIV

In the United States, observational studies of the quadrivalent LAIV have suggested a lack of effectiveness against H1N1 influenza A psm09 virus. In particular, the most recent observational data in the United States (for the 2013-2014 and 2015-2016 influenza seasons) revealed poor effectiveness of LAIV against H1N1 or less-than-expected effectiveness of LAIV against H3N2 during the drifted H3N2 season.

This observation stands in marked contrast to the current study, which used the trivalent LAIV. (The quadrivalent LAIV was not available in Canada in the 2013-2014 influenza season, Dr Loeb and colleagues note.)

"In contrast to the experience in the United States, we found that LAIV protection against H1N1 influenza A pdm09 virus in 2013 to 2014 was similar to that of IIV," the authors write in their discussion. "Observational data from 2014 to 2015 in the United States seem to show no difference in direct protection between LAIV and IIV."

However, on June 22, the United States Advisory Committee on Immunization Practices (ACIP) voted to recommend against the use of quadrivalent LAIV in the upcoming influenza season, on the basis of Centers for Disease Control and Prevention's (CDC's) observational data showing lack of effectiveness of LAIV.

Although a CDC employee served as chair of the data monitoring and safety board for the trial by Dr Loeb and colleagues, Lisa Grohskopf, MD, MPH, a medical officer at the CDC, explained to Medscape Medical News that members of a data monitoring and safety board cannot share data. The Canadian data were therefore not included in the ACIP's review.

When questioned as to whether the new data from Dr Loeb and colleagues would trigger a revisit of the ACIP recommendations, Dr Grohskopf said, "Part of the mandate of the ACIP is to review scientific data as it becomes available and consider how that data should shape vaccine policy."

She added that, "This process of continually looking at new data was what led ACIP to recommend against the use of LAIV during 2016-2017 because of data showing poor or lower-than-expected [vaccine effectiveness] of LAIV relative to IIV. ACIP has no plans to revisit their decision regarding the use of LAIV during the 2016-2017 season at this time; however, the decision was an interim one, meant to apply only to 2016-2017, so the issue will be brought up for deliberation before the 2017-2018 influenza season."

Dr Grohskopf also noted that the newly reported study examined the trivalent vaccine, whereas the CDC's data were specific to the quadrivalent vaccine (the formulation of LAIV used in the United States during the past three influenza seasons).

Is LAIV Effective?

The issue of effectiveness of LAIV is further complicated by the US Food and Drug Administration's (FDA's) recent approval of MedImmune's FluMist Quadrivalent LAIV for the upcoming influenza season.

The FDA addressed the controversial issue of effectiveness in a June 27 statement in favor of approval of LAIV for the 2016-2017 season: "This determination is based on FDA's review of manufacturing and clinical data supporting licensure noted above, the totality of the evidence presented at the ACIP meeting, taking into account the inherent limitations of observational studies conducted to evaluate influenza vaccine effectiveness, as well as the well-known variability of influenza vaccine effectiveness across influenza seasons. FDA continues to work closely with MedImmune to determine the cause of the lower than expected effectiveness of FluMist Quadrivalent observed in recent years."

The agencies have thus come to opposite conclusions about the use of LAIV. Dr Grohskopf explained that the difference is a result of the two agencies having unique mandates and considering different data in carrying out their roles.

"ACIP is an advisory committee charged with helping CDC carry out its responsibility of making public health recommendations using available data, including observational studies," noted Dr Grohskopf. "Its sister agency, FDA, evaluates new vaccines for safety and efficacy — a very different and important role," she explained.

Gathering Data for Review

Although ACIP requires new data to revisit its decision, gathering new data on LAIV in the United States may prove difficult. This is because the ACIP recommendation will likely result in decreased use of LAIV in the United States.

Nevertheless, the US Flu Vaccine Effectiveness network will continue to gather data on the effectiveness of both LAIV and IIV. In addition, as noted by the FDA, discussions are underway to identify which studies are needed to help determine the cause of the recent poorer effectiveness of LAIV against H1N1 influenza, as documented in the observational studies.

Dr Loeb receives grants from the Canadian Institute for Health Research, World Health Organization, and National Institutes of Health and personal fees from Sanofi Pasteur, Astra Zeneca, and Novartis Vaccines and Diagnostics. One coauthor reports honorarium from the Canadian Agency for Drugs and Technologies in Health outside the submitted work. The other coauthors and Dr Grohskopf have disclosed no relevant financial relationships.

Ann Intern Med. Published online August 16, 2016. Abstract

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