Hi Reddit! I’m Dave Topham and I’m a professor of Microbiology and Immunology at the University of Rochester Medical Center. I’m also a member of the Center for Vaccine Biology and Immunology and director of the New York Influenza Center of Excellence – one of five centers established by the National Institutes of Health to protect people against seasonal flu and future flu pandemics.
My lab, along with many others around the world, is pursuing a “universal” flu vaccine, one that would protect against most or all seasonal and pandemic strains of the flu virus. One of the most promising strategies is creating a vaccine that targets the “stalk” of a protein that covers the flu virus. It’s believed that the stalk stays relatively constant from one strain of flu to another. Directing a vaccine and the body’s immune response towards the stalk is a seemingly logical strategy for creating a shot that would provide broad protection.
In a study published in November in Scientific Reports we found that this strategy is a strong one, but isn’t completely bulletproof. We showed that the stalk can change under pressure from the immune system, although not as easily or frequently as other parts of the virus. The finding that it’s difficult, but not impossible to drive mutations in the stalk should be taken into account as we move forward with research and development.
I’m here to answer questions about universal flu vaccines, including the critical scientific questions that must be addressed to accelerate this research. I’ll start answering questions at 2 p.m. EST. AMA!
Do you think it would be actually possible to create a universal flu vaccine, due to the constantly mutating nature of the influenza virus? Also, how long do you think it will take your team to achieve this, and for how long would the vaccine be effective? Would it need to be updated yearly/regularly to include new strains of the virus like it currently is?
The goals set forth by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, is to develop a vaccine that protects at least 75% of the people from all influenzas, with immunity that lasts 5 years or more. There are many approaches being tested right now. Most target parts of the virus that are relatively conserved, that is they don’t mutate very often. The current seasonal vaccines, in contrast, are designed to focus the immune responses on the part of the virus that is used to attach to cells. This part of the virus is not conserved and changes quickly. So the hope is that by targeting one or more parts of the virus that don’t change, or are much harder to change such as the stalk of the HA instead of the head, then the vaccine will last longer and protect against more strains of the viruses.
I know it's isn't specifically science related, but since you are working on research that will have a profound effect on humanity if achieved. Is it the case that once the vaccine has been created you will sell to the highest bidder?
Obviously I know further research into drugs and vaccines cost billions upon billions of dollars. But is it achievable by selling the information to a company who has a bit more moral direction? (I know, I know, Big Pharma and morales is a bit of an oxymoron. But one can hope)
So my lab doesn’t actually design or develop vaccines. We study vaccines and how they work, or why they fail. We hope that by better understanding human immunity to influenza, that knowledge can be used to make better vaccines and also better predict who is most at risk of infection so we can intervene sooner. Our work is sponsored by the government (NIH) and we make what we learn publicly available at no charge. Typically, any new vaccine that is reliable has to eventually choose an industry partner to bring the vaccine to the market. Governments and big companies are the only one who have enough money to do this, and because it costs a lot, the drugs and vaccines need to cost a lot to make it worth while. Government can get a new vaccine started by paying for the research that goes into it, but it is just a fact of life that for a company to survive, it has to make money, or it goes away.
Thank you for taking time out of your day, professor.
Assuming you were to succeed, how would you overcome the public attitude toward flu vaccines even as it relates to vulnerable populations?
For example, the most recent University of Michigan National Poll on Healthy Aging found that only 73% of people ages 50 to 80 thought medical staff in nursing homes should be required to receive a flu vaccination.
How would you address that?
I think education is one way to address this problem. People take influenza for granted and it becomes part of life’s background. If people understood how much disease influenza really causes, and how much that costs in lives and dollars, perhaps their attitude would be different. That’s why I’m taking time today to answer questions ☺
What are the major scientific hurdles you're facing?
Many, many! I would say that one of the biggest hurdles is that we don't understand enough about human immunity to flu, how it gets established, how it changes over a lifetime, etc. We give a one-size-fits-all vaccine when maybe we need to have different vaccines for different people, such as for children versus the elderly.
How exactly do you or could you direct the immune response to the stalk? How would that work and why isn't it being done now? What's the barrier?
Actually there are many ongoing studies and trials of candidate vaccines that target the stalk. One idea is to make a vaccine that only contains the stalk, like a headless HA. This works in lab experiments, but we don't know if it will work the same in man. This partly because most people are already immune, which will affect how they respond.
Would this come with any known or potentially foreseeable side effects?
All vaccines can have side effects that tend to be minor such as pain at the site of injection. However, all vaccines in current use have been rigorously tested to avoid side effects, especially more severe ones. Any product that had severe side effects would not be licensed for use in healthy people.
Hi there, thanks for the AMA! I was told recently that, in the UK, the flu jab for this year is the same strain as the one for last year. Why is this the case, how often does this happen, and is there any major drawbacks / benefits?
There are actually four strains of flu in the flu vaccine, and H1, H3, and two flu B’s. Some of the strains stay the same from year to year, some have to be changed because the viruses going around have changed. The H3 component is by far the most variable, and this is the strain causing most of the infections this year. There are only two broad types of flu B and they change little from year to year. The major drawbacks of having to pick seasonal vaccine strains each year is the cost and getting it wrong. A universal vaccine would help fix that.
Why is the current strategy of making vaccines less effective?
This is my opinion, but I think our current strategy is one that tries to focus the immune response on a very specific target. The virus can then just easily change and escape. It is also hard to choose the right target every year, and sometimes we get it wrong. A universal vaccine would aim to generate a broad response that can protect against many strains of the virus.
What will your team do about dealing with the stalk changing under immune system response?
I think this is a phenomenon that needs a lot more study. We only tested one virus, and we need to test more to see how common or uncommon the changes we observed are.
What is the biggest challenge in creating a universal vaccine as opposed to an annual?
I know it’s looking at the viral core instead of the surface, but not much beyond that.
Also, has there ever been a push for a universal vaccine before? If no, why? If yes, what caused it to fail and what are we doing differently this time?
Thank you for your time and I look forward to learning!
I think the biggest challenge is choosing the right components to put in the vaccine. Should it be one protein or several? Both of these types of approaches are being tried. We as a field have been talking about universal flu vaccines for over a decade. It's just recently that NIH has made achieving a universal vaccine a major priority.
Hello from Rochester! What are some of the major costs associated with your research?
It is very expensive to recruit subjects, collect the samples, and process them. Never mind doing the experiments. We also need cutting edge technologies that are expensive to develop, but that is what is changing and improving our understanding.
I see that your goal is to target a component of hemagglutinin, could you fill us in on research that has been done on this before and how your project is different? Also exactly how similar is the structure you are targeting between different strains? And final question, why is HA the ideal target over the capsule or a conserved portion of neuraminidase?
There is a huge amount of research on immune responses to the hemagglutinin (HA). This is mostly because HA is the protein that antibodies to it blocks infection. Antibodies to other flu proteins can be protective too, but by different mechanisms. Part of the problem is that we use assays of virus infection, HA binding, and neutralization to test new flu vaccines. There are no widely accepted ways to reproducibly measure other forms of immune protection, so this makes it harder to develop and license alternative vaccines. My lab works on understanding why flu vaccines fail, which is a different perspective that studying how or why they work. By understanding the failures, we hope to find strategies to prevent them from happening. The work in the Scientific Reports paper showed that when we put pressure on a part of the virus that is supposedly conserved and unable to change, it can change. It just takes much longer for that to happen. This means targeting that part of the HA protein might be a good strategy to achieve longer lasting and more cross reactive protection. But it will not be permanent.
i'm wondering why a universal flu jab is a priority, when it seems a relatively harmless illness? is the mortality rate for flu a significant worry?
Flu is not a harmless illness, it’s just a familiar one. The Centers for Disease Control (CDC) estimate that influenza infects between 9.2 million to 35.6 million people, resulting in 140,000-710,000 hospitalizations and 12,000-56,000 deaths in the US alone every year. It tends to cause the most disease in the very young and very old, but we know of many examples of perfectly healthy young adults who get infected and are hospitalized or die. So please take flu seriously, not for granted. I think one of the problems is that it’s hard to distinguish real flu from other respiratory infections. It also doesn’t help to call other illnesses “flu” like “stomach flu”, which is a completely different virus. We spend millions of dollars every year to develop, test, and manufacture flu vaccines for both seasonal and potential pandemic viruses (H5, H7, etc.), because we are chasing an unpredictable pathogen. Universal vaccines would reduce the chasing that’s being done and perhaps those resources can be put to better uses.
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