Flu (influenza) is a serious disease caused by influenza viruses. Flu viruses change constantly. They are among the fastest mutating viruses known. These changes can impact how well the flu vaccine works, or can also result in the emergence of new influenza viruses against which people have no preexisting immunity, triggering a pandemic. Year round, scientists from CDC, World Health Organization (WHO), and other partners monitor the influenza viruses that are infecting people. These scientists study the viruses in the laboratory to see how they are changing.

CDC is using next-generation gene sequencing tools to analyze flu viruses as part of CDC’s Advanced Molecular Detection (AMD) initiative. The technology allows CDC to study more influenza viruses faster and in more detail than ever before. AMD technology uses genomic sequencing, high-performance computing, and epidemiology to study pathogens and improve disease detection. CDC is using this Next Generation-Sequencing (NGS) technology to monitor genetic changes in influenza viruses in order to better understand and improve the effectiveness of influenza vaccines.

To share more information about this revolutionary NGS technology and its impactful work, CDC expert John Barnes, PhD, Team Lead of the Influenza Genomics Team within the Virology, Surveillance, and Diagnosis Branch within CDC’s Influenza Division took part in a Reddit Ask Me Anything digital Q & A, to answer the public’s question on AMD technology and how these tools are helping to improve influenza virus monitoring and the development of better-performing influenza vaccines. This post includes some highlights from that discussion.

Question 1: What exactly does the AMD technology platform do that is different from the current approaches used to guide vaccine development? And what are the most common reasons that we “guess wrong” in terms of which viral strains will be responsible for the next season’s flu?

Dr. Barnes: One example of how AMD technology is used in vaccine development is to address mutations that may occur in vaccine viruses during growth in eggs used in the production of vaccine viruses. These mutations can change the vaccine virus so much that the immune response to vaccination may not protect as well against circulating viruses. This means that vaccinated people may still get sick. CDC is using AMD technology to try to solve this problem. Scientists are looking at the genetic sequences of 10 generations of H3N2 flu viruses as they grow and evolve in eggs. CDC will test all of the viruses to find out what genetic changes cause a good immune response and good growth in eggs. Once the “good” genetic changes are identified, CDC will then synthesize H3N2 viruses with those properties that can be used to make vaccine that offers better protection against H3N2 flu infection. One of the main reasons that the virus is challenging, is due to its’ RNA polymerase. The polymerase of influenza is very mistake prone and causes the virus to mutate rapidly. For example, in some years certain influenza viruses may not appear and spread until later in the influenza season, making it difficult to prepare a candidate vaccine virus in time for vaccine production. This can make vaccine virus selection very challenging. We are currently using AMD techniques to sequence all clinical specimens that come into the CDC to improve our ability to find and track mutations that may be of concern.

Question 2: Why are chicken embryos typically the go-to for flu vaccine cultivation?

Dr. Barnes: Thanks for this question – it’s one we get a lot!  Flu vaccines have been made using an egg-based manufacturing process for more than 70 years. In the past, when making a vaccine for production manufacturers utilized eggs as a safe host to make the vaccine and to provide high yield.  As birds are the natural reservoir host for flu, influenza typically grows well in eggs and maintains a safe distance between species you’re using to make the vaccine and the target.  Mammalian cell lines were subjected to extensive safety testing to establish a cell line that is human pathogens free, while maintaining sufficient vaccine yield. You can learn more about how AMD technology is improving the development of flu vaccines made using egg-based technology, here.

Question 3: What about the flu virus causes it to mutate so quickly from year to year requiring a new vaccine every season? For example with chickenpox there is one virus and one vaccine, why then with the flu are there countless strains and a new vaccine every year?

Dr. Barnes: As you know, influenza is a virus and can only replicate in living cells. Influenza viruses survive by infecting host cells, multiplying, and then exiting host cells. The enzyme influenza uses to copy itself is very error prone which causes the virus to rapidly mutate. Each host has its own defense mechanisms and these defenses are collectively referred to as environmental pressures. It’s difficult to predict how a virus will mutate when attempting to get around a host’s immune defenses, but the changes can happen rapidly, as you said.

Because flu viruses are constantly changing, the formulation of the flu vaccine is reviewed each year and sometimes updated to keep up with changing flu viruses. More information about how influenza viruses can change is available here.

Question 4: Do you have any insight on the universal vaccine that was developed?

Dr. Barnes: Great question! Yes, I can provide some insight. A longer-term goal for seasonal flu vaccines is the development of a single vaccine, or universal vaccine, that provides safe, effective, and long-lasting immunity against a broad spectrum of different flu viruses (both seasonal and novel). Right now, CDC is a part of an inter-agency partnership coordinated by the Biomedical Advanced Research and Development Authority (or BARDA) that supports the advanced development of new and better flu vaccines. These efforts have already yielded important successes (i.e. a high dose flu vaccine specifically for people 65 years and older that creates a stronger antibody response), but a part of this effort is the eventual development of a universal vaccine. A number of government agencies and private companies have already begun work to advance this type of vaccine development, but, as you can imagine, this task poses an enormous scientific and programmatic challenge.    

Question 5: How would you convince someone who is staunchly against flu vaccines that they’re a good thing?

 Dr. Barnes: Help address misconceptions about the flu. Remind people that a flu shot cannot cause flu illness. They should understand that anyone can get the flu, and each year, thousands of people in the United States die from flu, and many more are hospitalized.  It’s important to stress that the flu vaccine can keep people from getting flu, make flu illness less severe if they do get it, AND keep them from spreading flu to their family and other people that could be at high risk of severe flu complications.

Interested in learning more? Check out Dr. Barnes’ full Reddit AMA here.

John Barnes, Ph.D., is Team Lead of the Influenza Genomics Team (IGT) at the Virology, Surveillance, and Diagnosis Branch of the CDC’s Influenza Division. He earned his Ph.D. degree in Biochemistry and Molecular Biology from University of Georgia in Athens, Georgia. Dr. Barnes began his career at CDC in the Influenza Division in 2007 after working at a postdoctoral fellow at the Emory University Department of Human Genomics. His current work includes managing a staff of nine to serve the sequencing and genetic analysis needs of the Influenza Division. Current numbers of viruses sequenced by the IGT make CDC’s Influenza Division the largest contributor of influenza sequence data among the WHO Influenza Collaborating Centers.