Lab Matters Winter 2018 - Page 10

feature “We need a better understanding of the different immune mechanisms and how they can protect against the virus.” —Jackie Katz, PhD Seeking A True Game Changer The holy grail of influenza prevention and control is a universal flu vaccine that would provide long-term immunity against all influenza viruses. And that is still a “good way off,” said Jackie Katz, PhD, head of the CDC-based WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza. Instead, current influenza vaccines are strain-specific, targeting the viruses projected to predominate six to nine months or so after WHO issues its vaccine recommendation for the Northern Hemisphere in February and for the Southern Hemisphere in September. Those recommendations are based on a painstaking review of “over a thousand pages” of antigenic, genetic and other data from WHO collaborating centers and partners, including mathematical modelers. Yet it is always a gamble. Katz said, “Current vaccines are based on an understanding of one type of immunity—a neutralizing antibody directed against the head of the hemagglutinin.” And that spiky protein head, she said, “is a moving target,” subject to continual change (“antigenic drift”) as a result of mutations that occur while the virus resides in host organisms and while it is grown in chicken eggs during the months- long vaccine production process. “I think in most years we’ve had a good antigenic match,” said Katz. “But we’ve been wrong five times in the last 25 years for the H3N2 subtype, the most variable human influenza A virus, with the most recent mismatch in the 2014-15 season.” To up the odds of success, WHO authorities have begun issuing recommendations for the traditional trivalent (three-strain) vaccine, plus 8 LAB MATTERS Winter 2018 a quadrivalent (four-strain) vaccine. Thus, today 75% of US flu vaccines are quadrivalent, including two strains of influenza B (one from the Yamagata lineage and one from the Victoria lineage) and two strains of influenza A (typically an H3N2 virus and an H1N1 virus). In addition, some years ago, the US Biomedical Advanced Research and Development Authority (BARDA) jumpstarted an effort to grow influenza viruses in cell culture to avoid the genetic and antigenic changes that may be introduced into egg-based vaccines. BARDA also invested in bringing a recombinant flu vaccine to the market, another non-egg-based technology. But to achieve a true game-changer—a universal vaccine—scientists must think outside the box. “We need a better understanding of the different immune mechanisms and how they can protect against the virus,” said Katz. “The strategy is to focus vaccine response on something that doesn’t change as much [as hemagglutinin].” So far, she said, “We’re still just scratching the surface.” In some ways, the 1918 pandemic was unique. Nearly half the flu-related deaths were in adults 20–40 years of age, and more than 99% were among those under age 65. The virus attacked in three waves within a 12-month period. And WWI conditions—overcrowding, mass movements of civilians and military personnel, and reluctance to shut down wartime production facilities—worked in the virus’s favor. “Today we have vaccines,