Jul 18, 2011 (CIDRAP News) – In an effort to overcome the difficult problem of predicting which influenza B strain will circulate in any given season, MedImmune has filed for US approval of a quadrivalent (four-strain) flu vaccine containing two influenza B strains.
The idea of a quadrivalent flu vaccine has been discussed for several years, but MedImmune's application apparently is the first attempt to license such a vaccine in the United States.
MedImmune's vaccine is a quadrivalent version of its licensed trivalent nasal spray vaccine, FluMist. The company, based in Gaithersburg, Md., announced today that the Food and Drug Administration (FDA) had received its supplemental license application.
Seasonal flu vaccines for many years have targeted three flu subtypes: A/H1N1, A/H3N2, and B. But in recent years type B viruses from two different lineages—Yamagata and Victoria—have circulated at varying and unpredictable levels.
Because of production timelines, the strains to be used in seasonal flu vaccines must be chosen more than 6 months before the season starts. That requires flu experts to bet on which strains will be most common during the season, and they have had spotty success in picking the type B lineage. Vaccines targeting one B lineage have provided limited protection against the other, which has fueled interest in including both lineages in the vaccine.
The Centers for Disease Control and Prevention has reported that both B lineages have circulated during most of the past 10 seasons, according to a MedImmune press release.
"In the United States, in a recent 10 year interval of influenza seasons, the predominant circulating influenza B lineage was different in 5 seasons from the one selected for inclusion in the vaccine," Robert Belshe, MD, director of the Center for Vaccine Development at Saint Louis University, commented in the release.
In clinical trials in adults and children, the quadrivalent live attenuated vaccine (Q/LAIV) compared well with two different versions of trivalent FluMist, the company said.
"The quadrivalent vaccine induced immune responses to both B strains and the immune responses for all of the four strains in the vaccine were comparable to the immune responses induced by the trivalent vaccines," MedImmune said. "Additionally, Q/LAIV had a comparable safety profile to the trivalent FluMist formulations in the indicated FluMist population (eligible individuals 2-49 years of age)."
MedImmune spokesman Tor Constantino said he could not give further details on the trial results, as they are currently being reviewed for submission to a journal. "However, it's fair to say that the results of the Q/LAIV trial warranted further progression and development of this potential vaccine," he told CIDRAP News.
Flu experts say type B viruses in general cause less severe disease than type A, but they can cause severe cases.
"We believe that the inclusion of an additional B strain in an annual influenza vaccine could provide a direct health benefit to individual vaccine recipients in the event that the correct B lineage either is not selected for inclusion in a trivalent vaccine, or if both lineages co-circulate," Filip Dubovsky, MD, MedImmune's vice president of clinical development, commented in the press release.
In recent years the FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC), which recommends the flu strains to include in the seasonal vaccine, has discussed including two B strains, but so far the panel has not recommended that step.
FDA spokesman Paul Richards could not give an immediate answer today on whether a specific VRBPAC recommendation would be a prerequisite to licensing of MedImmune's quadrivalent vaccine.
Richards noted that, since the vaccine strains change in most years, flu vaccine manufacturers submit a supplemental license application each year for their seasonal vaccine. "If a company has a vaccine with a second B or a fourth strain, it would be a similar process," he said.
Richards said he couldn't estimate how long the FDA review of MedImmune's application might take.
Robert B. Couch, MD, a flu vaccine expert at Baylor College of Medicine in Houston, said he was a little surprised to learn about MedImmune's application. "MedImmune seems to be first in line," he commented. He is Distinguished Service Professor in Baylor's Department of Molecular Virology and Microbiology.
Couch said the idea of including two B strains "has been kicked around for 3 or 4 years. It's increasingly materializing into people working on a solution."
"The important data will be in children—that's where the major differences in responses have been," Couch commented. "Adults tend to have cross-reacting responses to a varying degree, so the need to have a response to both vaccine strains is most important in children."
Sanofi Pasteur, the largest supplier of flu vaccines in the United States, is developing a quadrivalent version of its Fluzone vaccine, company spokeswoman Donna Cary said today, but the firm has not yet announced a license application.
"We started enrolling an adult and a pediatric trial last season," Cary said. "The adult trial was fully enrolled, and the pediatric trial is ongoing this season." No results have been released yet.
See also:
Jul 18 MedImmune release
Jan 16, 2009, CIDRAP News story "Experts consider 4-strain flu vaccine to fight B viruses"
