TMC PULSE

t m c » p u l s e | o c t o b e r 2 0 1 6 7 What you're really trying to do is to grow the virus in eggs in high content, purify it, then inactivate it. — PEDRO PIEDRA, M.D. Professor in the Department of Molecular Virology and Microbiology at Baylor College of Medicine Baylor is one of more than 100 international influenza centers that conducts flu surveillance year-round. The job of these centers is to collect, test and analyze virus samples to help determine which flu strains are making people sick and identify any patterns related to their range and distribution. The centers then send what is called "representative" viruses to five World Health Organization Collaborating Centers for Reference and Research on Influenza. The center for the U.S. is located at the CDC in Atlanta, and the other four are located in London, Melbourne, Tokyo and Beijing. In February and September, leaders from these centers meet with experts worldwide to review the results of the surveillance and discuss their rec- ommendations for the makeup of the approaching season's vaccine. Based on these recommendations, and with the previous year's vaccine efficacy in mind, it is up to each individual country to decide which strains will be included in its vaccine. The final say for the U.S. lies with the Food and Drug Administration (FDA). Once the decision is made, manufacturing begins immediately. First, Piedra explained, the FDA supplies "seed viruses" to private sector manufacturers, who are responsible for making all the flu vaccines in the coun- try. The most common manufacturing method occurs through egg-based production, which involves taking the seed virus and injecting it into a fertil- ized chicken egg where it can multiply. After an incubation period, the virus is harvested and scientists isolate the antigen and package it in the form of the flu shot. "They are basically very special farms that are highly regulated. The eggs are as clean as they can be," Piedra said. "What you're really trying to do is to grow the virus in eggs in high con- tent, purify it, then inactivate it." The entire process takes time— six months minimum—and requires a vast number of eggs. It is by far the most prevalent method in practice, but other approaches do exist, including cell-based production, which uses mammalian cells as a vector for rep- lication rather than eggs, as well as a technique involving recombinant DNA technology and the cells of insects. It's big, important business and, unfortunately, not always on target. In January 2015, the CDC determined that the 2014-2015 season's flu vaccine was only 23 percent effective. As it turns out, a minor strain had become a major player well into vaccine production, and it was too late to do anything about it. "Many times the prediction is correct, but sometimes the prediction is not," Piedra said. "During the 2014-2015 season, the major circulating virus was H3N2 and it had significantly drifted from the strain in the vaccine. When the decisions were being made as to which components were to be included, the H3N2 variant had just been identified, and that particular variant accounted for about one percent of all H3N2s. Then we saw that it persisted and seemed to be increasing, but at that point we couldn't make it a vaccine component." Still, Piedra said, it was worth get- ting the flu shot that season. Although the H3N2 component was not effec- tive, the B component and the H1N1 components worked well. And, while 23 percent efficacy is not ideal, it's also better odds than nothing at all. That's why, when the CDC's Advisory Committee on Influenza Practices (ACIP) announced that the live attenuated vaccine (commonly known as FluMist) should not be offered this year due to concerns about its effectiveness, Piedra was disap- pointed. For years, the nasal spray vac- cine offered an ideal alternative to the dreaded "shot," increasing vaccination rates among younger children. "From a pediatrician's perspective, it's sad," he said. "I recently heard some- one refer to school children as a biohaz- ard, and it's true. They get infected with everything. They spread it within their units of friendship and acquaintances, and they bring it to the family. Children really are an excellent vector for trans- mission of influenza." According to Piedra, the ACIP's rec- ommendations were based on internal data of flu shot effectiveness within certain populations. For the past three years, the live attenuated vaccine had not worked as well as the shot. "This has brought out a debate, because there are other countries, like our northern borders in Canada, where the live attenuated vaccine has been demonstrated during those same years to be effective. The same thing is true for the U.K.," Piedra said. "So it's unfor- tunate and we will see what impact it has." It seems millions of children will need to shut their eyes, hold their breath, and muster some extra courage this year. Experts predict the 2016-2017 flu season will be active, and Piedra urges individuals to take the time to get vaccinated as soon as possible. "Now is the time to do it," he said. "Don't wait until flu is here." Credit: Associated Press

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