SILVER SPRING, MD. — The idea of adding a second influenza type B strain to the seasonal influenza vaccine was met with generally positive responses by vaccine experts who discussed the utility of a quadrivalent vaccine at a meeting convened by the Food and Drug Administration.
The FDA's Vaccines and Related Biological Products Advisory Committee discussed the pros and cons of adding a second B component to the vaccine, but it did not vote on the issue or make any formal recommendations to the FDA.
Since 2000, the two cocirculating lineages of influenza B viruses (B/Yamaguchi and B/Victoria) have become more antigenically distinct, raising the issue of whether adding a second B strain to the seasonal flu vaccine would have a positive public health benefit, Rakesh Pandey, Ph.D., of the FDA's Division of Vaccines and Related Products Applications, said at the meeting.
Cocirculation of the two B lineages means that “some degree of mismatch between a vaccine and circulating strain is inevitable,” which can reduce the effectiveness of the trivalent vaccine as well as public confidence in the vaccine, pointed out Carrie Reed, D.Sc., of the Centers for Disease Control and Prevention, who also spoke at the meeting.
The current trivalent seasonal flu vaccine includes two influenza A strains (H1N1 and H3N2) and a B strain.
Among the issues that need to be considered before a second B strain is added include the clinical data needed to establish the safety and immunogenicity of a vaccine with two B strains; the public health impact and cost; and whether better coverage of influenza B would make up for potential delays in manufacturing and vaccine availability, according to Dr. Pandey. Another issue is whether the quadrivalent vaccine could be targeted to subpopulations, such as children and the elderly.
B strains are harder to grow than A strains, which could delay the availability of the influenza vaccine. However, the manufacturing capacity of influenza vaccine has markedly increased over the past 4–5 years, so manufacturers may be able to adjust to adding another component to the vaccine, Dr. Pandey noted.
Dr. Reed presented the results of a CDC analysis, conducted at the request of the FDA, on the impact that a second B strain would have had on the last 10 flu seasons in the United States. The analysis used a model that averaged all ages, and calculated the burden of influenza during each season by type, subtype, and lineage. The model did not include cost estimates.
Considering that B viruses do not grow as well as A viruses, about 25% less vaccine would be produced if a second B component were added to the vaccine, she said. This could have a negative impact on seasons in which supply of the influenza vaccine is similar to the demand, but for seasons in which supply exceeds the demand, the amount of quadrivalent vaccine available would still exceed the amount of vaccine administered, she pointed out.
For example, during the 2007–2008 influenza season, type B strains accounted for 29% of the virus tested, and 98% of the B strains tested were not the lineage included in that season's vaccine. Based on these data, the CDC analysis estimated that there would have been more than 1 million fewer cases of influenza, almost 7,500 fewer influenza-related hospitalizations, and about 320 fewer deaths if a quadrivalent vaccine had been available, Dr. Reed said. There was an excess supply of vaccine that season, so the lower number of vaccine produced would not have had a negative impact on coverage, she added.
During 2005–2006, about 20% of the circulating strains were influenza B viruses, and 78% of the strains were not the lineage in the vaccine. There would have been fewer doses of a quadrivalent vaccine, so an estimated 8% fewer people would have been vaccinated. Because of a better match provided by a quadrivalent vaccine, there would be an estimated 440,841 fewer cases because of the better match, but 298,204 more cases because of less coverage—a net benefit of 142,637 fewer cases, she said.
But for a season like 2004–2005, when there were problems with manufacturing that affected the supply and when the supply was similar to the demand, an estimated 15% fewer people would have been vaccinated if the vaccine had been a quadrivalent one. That season, 25% of the circulating strains were type B, and 26% of those B strains were the lineage not included in the vaccine. Considering these data and the supply issue, there would have been an estimated net increase of 151,566 cases of influenza if a quadrivalent vaccine had been used, according to Dr. Reed.