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Man Versus Flu: the Search for a Universal Influenza Vaccine Let Me Tell You the Secret That Has Led Me to My Goal: My Strength Lies Solely in My Tenacity

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Man Versus Flu: the Search for a Universal Influenza Vaccine Let Me Tell You the Secret That Has Led Me to My Goal: My Strength Lies Solely in My Tenacity BioFocus INDUSTRY INSIGHT Man Versus Flu: The Search for a Universal Influenza Vaccine Let me tell you the secret that has led me to my goal: My strength lies solely in my tenacity. — Louis Pasteur by KEITH BERMAN, MPH, MBA NO ONE CAN argue that there are not plenty of options these days for annual immunization against the flu. For the 2013-14 season, seven manu - facturers — up from four a decade ago — are offering a smorgasbord of inactivated and live-attenuated and recombinant, trivalent and quadriva - lent, standard and high-dose, and intramuscular and intranasal and intradermal flu vaccines. Yet despite the panoply of choices, influenza remains a serious public health threat. The most recent 2012-13 flu season presents a sobering reminder of the limits of our current vaccine technology. While flu vaccines were 56 percent effective for all recipients, they were just 9 percent effective for persons age 65 and older. The number of flu- related pediatric deaths during last year’s flu season was the highest reported since data collection began in 2004. 1 The hospitalizations avoided and lives saved by current-generation flu vaccines unquestionably justify the annual effort and cost of hunting down target strains, then manufacturing and administering around 135 million vac - cine doses this season. 2 But this winter, tens of millions of Americans will come 48 BioSupply Trends Quarterly • October 2013 INDUSTRY INSIGHT down with the flu (including many, of systems can “remem ber” and generate As a growing portion of the flu- course, who neglect to get their annual neutralizing antibodies to similar- infected — or vaccinated — population flu shot), millions of workdays will be look ing flu strains has bolstered builds effective neutralizing antibodies lost, as many as 200,000 or more people enthu siasm about the prospects for a against the prevalent influenza virus may be hospitalized, and thousands will universal vaccine or vac cine cocktail. strains, natural selection favors new die from flu-related complications. variants that are capable of escaping The obvious need remains for “a Influenza Viruses as Escape Artists host immunity by virtue of their altered vaccine that you don’t have to give Despite their different production HA protein structure. Thus, we see every year that works better,” said Dr. processes, presentations and delivery antigenic drift of the flu viruses that circulate over the course of each season. The greater the mismatch between the drifted virus strains and the early Influenza viruses exploit three potent virulent strains against which the season’s flu vaccine was manufactured, evolutionary strategies that enable them the more the efficacy of the vaccine is diminished. to return to infect us again and again. Periodic flu pandemics occur when entirely new influenza virus subtypes are created by genetic reassortment Joseph Bresee, a senior epidemiologist options, all licensed influenza vaccines when two different viruses co-infect the in Centers for Disease Control and work by inducing protective humoral host cell. Unlike most viruses that have Prevention’s (CDC’s) Influenza Division. 3 immunity against antigenic targets on a single RNA strand, the flu virus “Among the two dozen vaccine-pre - the globular “head” portion of hemag - includes eight RNA strands to encode ventable diseases, including measles, glutinin (HA), a surface glycoprotein its genome. When all those strands mumps, polio, smallpox and hepatitis, that the virus uses to attach itself to intermix, a novel “reassortant” progeny seasonal influenza is the only one for res piratory tract and other host cells virus can be created that never existed which a new vaccine is recommended (Figure 1). When exposed to the circu - before. The H1N1 strain that caused the every year. A more efficient approach is lating live flu virus, the immunized 2009 swine flu pandemic, for example, long overdue,” noted Dr. Anthony individual rapidly produces specific was a complex reassortant of avian, Fauci, director of the National Institute antibodies that inhibit virus infection of Allergy and Infectious Diseases. 4 by blocking HA attachment to our cells. Possibly the best evidence for the Yet, when the next flu season rolls fea sibility of a longer-acting, broadly around, without immunization Figure 1. Stucture of the Hemagglutinin protective “universal” flu vaccine comes against the new epidemic strain, we are (HA) Protein from a natural experiment — the once again susceptible to contracting sur prisingly mild 2009 H1NI flu the illness. pan demic. Antigenically distinct from Influenza viruses exploit three potent recently circulating H1N1 seasonal flu evolutionary strategies that enable them viruses, that H1N1 virus turned out to to return to infect us again and again. be a distant relative of the virus The error-prone replication of viral respon sible for the devastating 1918 RNA strands in the human or other Spanish flu pandemic. A new analysis by mammalian host cell generates sponta - scientists at the Wistar Institute has neous mutations that translate into revealed that people of different ages changes focused in particular in the experienced vastly different antibody polymorphic head portion of the viral response rates to the 2009 H1N1 HA surface protein. Antigenic shift pan demic virus, depending on whether occurs when significant mutations they were exposed to a seasonal H1N1 create new flu viruses that are poorly virus many decades earlier. 5 This new recognized by large seg ments of the understand ing that our immune population. BioSupply Trends Quarterly • October 2013 49 BioFocus INDUSTRY INSIGHT Figure 2. Influenza Virus: Potential Target Antigens for a Universal Vaccine rate one or more of the following three viral proteins: • Hemagglutinin A (HA) stem region. Also referred as the HA stalk, this region of the HA glycoprotein is highly con - served. One group has designed a novel vaccine that includes the stem portion of HA without the globular head; mice vaccinated with this “headless HA” were completely protected against a lethal influenza virus challenge. 7 Separately, researchers at the Scripps Research Institute report isolating a monoclonal antibody (MAb) that rec - ognizes a highly conserved epitope on the stem region of HA and neutralized influenza virus by preventing virus-host membrane fusion. 8 They and others have subsequently identified other MAbs that target the HA stem region, creating an entirely separate theoretical opportunity to produce a MAb cocktail that could be used to provide passive immunity in cases of severe influenza. 9 • Matrix protein 2 (M2e). This highly conserved external domain of this human and swine influenza viruses Universal Flu Vaccine Candidates influenza A surface glycoprotein plays a that further reassorted with a The functional premise of most key role in virus morphogenesis and Eurasian swine flu virus. 6 But as a development-stage universal influenza assembly. On hopes that it can induce growing share of the population was A and B vaccines is simple: Induce highly cross-protection against different sub - exposed to it, immune selection resulted in antigenic drift of the 2009 H1N1 virus, resulting in its transition to a seasonal flu virus. By the end of the last decade, Thus, the flu virus rebounds to create new epidemics each year by continu - cautious optimism was being expressed ally changing its antigenic presenta - tion, which both necessitates the annual at research conferences that the first licensure and production of new vac - cines, and leaves us highly vulnerable to the next flu pandemic. But encour - universal vaccine could be available aging recent findings reported by some laboratories have raised hopes in as little as five years. that a long-dreamed-about strategy of targeting highly conserved viral proteins could yield broadly protec - cross-reactive antibodies against highly types, M2e has been selected for a number tive “universal” vaccines that confer conserved antigenic targets across dif - of universal influenza A vaccine candi - long-term protection against both ferent influenza virus subtypes and dates. To improve its immunogenicity, drifted and pandemic influenza A strains (Figure 2). Most promising several groups have linked M2e to such and B. development-stage vaccines incorpo - platforms as hepatitis B virus core, 50 BioSupply Trends Quarterly • October 2013 S SHE KEEPS YOUR PRESCRIPTIONS UP-TO-DATE THIS FLU SEASON, ASK YOUR SHE ANSWERS PHARMACIST YOUR HEALTH ABOUT FLUCELVAX QUESTIONS (INFLUENZA VIRUS (WITH A SMILE) VACCINE) SHE EVEN GIVES YOU YOUR FLU SHOT EVERY YEAR FLUCELVAX (Infl uenza Virus Vaccine) was the fi rst FDA-approved cell-based fl u vaccine made with an advanced scientifi c process. It does not contain antibiotics. And it doesn’t contain preservatives. FLUCELVAX is for people 18 years or older. To fi nd out where to get your FLUCELVAX shot, go to FLUCELVAX.com. What is FLUCELVAX® (Infl uenza Virus Vaccine)? What are the most common side effects FLUCELVAX (Infl uenza Virus Vaccine) is a vaccine that of FLUCELVAX (Infl uenza Virus Vaccine)? helps protect against infl uenza (fl u). • pain or redness where you got the shot FLUCELVAX is for people aged 18 and older. Vaccination • headache with FLUCELVAX may not protect all people who receive • tiredness the vaccine. • muscle aches • feeling unwell (malaise) Important Safety Information for FLUCELVAX These are not all of the possible side effects of Who should not get FLUCELVAX? FLUCELVAX. You can ask your healthcare provider for • You should not get FLUCELVAX if you have had a severe a complete list of possible side effects. allergic reaction to any of the ingredients in the vaccine Ask your healthcare provider for advice about any side Who may not be able to get FLUCELVAX? effects that concern you. You may report side effects to Tell your healthcare provider if you: the Vaccine Adverse Events Reporting System (VAERS) by • have ever had Guillain-Barré Syndrome (severe calling 1-800-822-7967 or by going to http://vaers.hhs.gov.
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