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Timing is critical with this unique influenza season
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It is the start of another new influenza season. For my more than 30 years in vaccine research, this has always been a time of anticipation.
Many of my early years were marked by the onset of a vaccine trial to study the safety and immunogenicity of a new seasonal influenza vaccine, such as the live-attenuated vaccine. More recent years have signaled the start of influenza effectiveness trials to evaluate the effect of the influenza vaccines on disease burden.
As a pediatrician practicing infectious diseases in a large referral center, every year a number of children will be hospitalized when influenza hits, and some will succumb to its complications. Thus, each season poses a number of conflicting scenarios.
First, I don’t want the influenza season to come too soon, before everyone is vaccinated. Second, I want the circulating strain to match the strains included in the vaccines that I am testing. And, third, from the research perspective, I am challenged with needing to make an educated guess on the robustness of the upcoming season in order to best plan my approach to measure the effect of the vaccine. Of course, the pediatrician in me hopes the influenza season will be mild, as fewer influenza-related hospitalizations and deaths are the goal. Maybe these challenges explain why my hair is now gray and my brow is furrowed. Influenza research is not for the faint of heart.
First of it’s kind
Personally, this influenza vaccination season is going to be somewhat different from most of them before. Our group at Vanderbilt has been tasked, as part of our NIH-funded Vaccine and Treatment Evaluation Unit (VTEU) contract, to conduct a large safety and immunogenicity study of the influenza A(H7N9) vaccine. This avian strain was first detected in China last spring and has thus far infected 135 people, most of whom have had contact with poultry. Most of the infected patients have had severe respiratory infections, and 44 people have died — or 32% of those who had recognized infections due to this virus. Although the median age of those stricken with H7N9 virus has been 58 years, four cases were confirmed in children.
United States health policy leaders have decided that the nation must prepare for the potential pandemic spread of this new influenza strain, and we are responding to this challenge. Researchers from seven other VTEU sites will also participate in this study. It is anticipated that 1,000 adults will enroll in the initial trials. Although it is unknown whether this H7N9 influenza strain will ultimately spread globally, there are a number of indications that it is a real possibility. Intensive ongoing studies of the transmission patterns in animals are being conducted.
A recent report from China indicates that the H7N9 virus isolated from humans replicates in both the upper and lower respiratory tract in ferrets, an excellent model for human influenza, and is efficiently transmitted between ferrets. Pigs can also be infected with these H7N9 strains and shed virus for periods as long as 6 days, but transmission to other animals was not seen, according to a study by Zhu and colleagues. In addition, the recent report of apparent human-to-human transmission of H7N9 virus from father to daughter and their subsequent deaths, adds even greater concern.
Dr. Chen Hualan, director of the Chinese National Avian Influenza Reference Laboratory, recently commented in an editorial in Science that H7N9 appears to infect humans “much, much more easily than H5N1.” In addition, birds infected with H7N9 do not appear ill. Thus, it is impossible to selectively identify such birds for culling or to use selective isolation techniques.
Finally, as our H7N9 studies progress through the fall, additional concern must also be raised about the natural circulation of H7N9 in China and potentially in other parts of the world. Influenza circulation always increases when the weather turns cooler, and transmission is enhanced when people are in closer contact in dry indoor settings.
Complex issues related to vaccine studies
As many are aware, there is a raging controversy about restrictions on the genetic manipulation of avian influenza strains in the laboratory, resulting in the halting of all studies with H5N1 strains funded by the NIH for more than a year. Although the ban has been lifted, the US government has recently announced a new comprehensive review process guiding such experiments. An understanding of the genetic underpinnings of what is required to make an influenza virus transmissible is extremely important and has obvious implications for vaccine development. However, concerns about the potential uses of a virulent virus for bioterrorism must be taken seriously. These are interesting times. It is very important that we develop and perfect avian influenza vaccines, but such genetic studies should be carefully monitored and reported.
Avian influenza vaccines are generally very poorly immunogenic in humans and require large amounts of antigen to induce an adequate antibody response. The addition of adjuvants to avian influenza strain vaccines resulted in marked potentiation of the immune responses in prior studies. Several adjuvants will be evaluated in our studies, and their contributions to the safety and immunogenicity of the avian influenza strains will be meticulously assessed.
Challenges that lie ahead
This will be a memorable influenza season, indeed! We can only hope that H7N9 viruses will not find a way to become widely transmissible in humans. Regardless, we are aiming to be prepared with a safe and highly immunogenic vaccine. Timing is critical — both for vaccine testing and to enable production for all the global community. These are daunting challenges, but ones that must be addressed.
References:
Hualan C. Science. 2013;341:122-125.
For more information:
Kathryn M. Edwards, MD, is the Sarah H. Sell and Cornelius Vanderbilt Chair in Pediatrics at the Vanderbilt University School of Medicine, Nashville, Tenn. She is also a member of the Infectious Diseases in Children Editorial Board. She can be reached at: Vanderbilt Vaccine Research Program, 1161 21st Ave. South, CCC 5311 MCN, Nashville, TN 37232.
Disclosure: Edwards reports no relevant disclosures.