The first influenza vaccine that contains a second influenza B strain, in addition to two influenza A strains and one influenza B strain, has been approved for people aged 2 through 49 years, the Food and Drug Administration announced on Feb. 29.
The quadrivalent vaccine is an intranasal vaccine, similar to FluMist, the trivalent influenza vaccine licensed as a seasonal influenza vaccine for individuals aged 2 through 49 years. The quadrivalent vaccine contains two strains of type A influenza (A/H1N1 and A/H3N2) and two type B lineage strains, "which increases the likelihood of adequate protection against circulating influenza B strains," the FDA statement announcing the approval said.
Cynthia Goldsmith/CDC photo #10073
This negative-stained transmission electron micrograph (TEM) depicts the ultrastructural details of an influenza virus particle, or "virion."
"A vaccine containing the four virus strains most likely to spread and cause illness during the influenza season offers an additional option to aid in influenza prevention efforts," Dr. Karen Midthun, director of the FDA’s Center for Biologics Evaluation and Research, said in the statement. She pointed out that influenza B-related illness "affects children, particularly young and school-aged, more than any other population."
The new vaccine will be marketed as "FluMist Quadrivalent" by MedImmune LLC, which also markets FluMist, the trivalent intranasal influenza vaccine.
The safety and effectiveness of the Flu Mist quadrivalent vaccine is supported by studies of the trivalent formulation conducted in the past, as well as three new studies of the quadrivalent vaccine in about 4,000 children and adults in the United States, which "demonstrated that the immune responses were similar between FluMist Quadrivalent and FluMist," the FDA statement said. Adverse reactions associated with both vaccines were similar. A runny or stuffy nose in children and adults and headache and sore throat in adults were the most common adverse reactions reported, according to the FDA.
The other seasonal influenza vaccines that are licensed by the FDA contain the three strains only. At a meeting of the FDA’s vaccines advisory panel, held the day before the FDA announced the FluMist Quadrivalent approval, representatives of several manufacturers said that they had completed trials of quadrivalent formulations of their trivalent vaccines and had either filed or planned to file for approval with the FDA and anticipated approval in time for the 2012-2013 influenza season.
At that meeting, held annually to recommend the two influenza A and one influenza B strains to be included in the vaccine in the United States for the upcoming season, panelists pointed out how challenging it is every year to choose which B strain to recommend, based on the different B strains that are circulating worldwide, and described choosing the B component as a "gamble" and a "crapshoot."
"Flu B has been a dilemma, and I do look forward to having a quadrivalent so that our crapshoot is not so poor," one of the panel members, Dr. Pedro Piedra, professor in the department of molecular virology and microbiology, Baylor College of Medicine, Houston, said at the meeting.
"I’m really gratified to hear of all the progress that’s been made by the manufacturers in developing the quadrivalent product and I look forward to the end of this annual conversation about which B [strain] should go into the vaccine," said another panelist, Dr. Melinda Wharton, deputy director of the Centers for Disease Control and Prevention’s National Center for Immunization and Respiratory Diseases. "I always feel like we’re having to make a decision that has a pretty high probability of being wrong on these B strains," she added. (FDA panelists are cleared of potential conflicts related to the topic of the meeting.)
At that meeting, the panel recommended that the influenza B strain be replaced with a B/Yamagata lineage strain, a switch from a Victoria lineage B strain that has been in the vaccine for several years. But they were less confident about this recommendation than they were with their recommendations for the two influenza A strains.
During this flu season in the United States, which has started later than usual and with less activity than previous years, there is evidence that influenza B viruses from both lineages have been circulating. At the panel meeting, Dr. Lisa Grohskopf of the CDC’s influenza division, said that of the 397 influenza viruses tested at the CDC this season, 48 (12%) have been influenza B strains. About half of those have been a B/Victoria lineage strains and most of those match the strain in the current influenza vaccine, but the rest have been a Yamagata lineage strain, not included in the current vaccine. But Dr. Grohskopf, who was not a panelist, added that there have not been many B viruses available for testing in the United States.