What’s going on in the vaccine space right now?

Rebecca Aris interviews Nikolai Petrovsky


pharmaphorum’s Managing Editor, Rebecca Aris, interviews Nikolai Petrovsky on current issues and challenges facing the vaccines space right now.

What challenges are currently facing the vaccine space? What therapeutic areas hold the most promise for vaccines right now? And where next for vaccine development formulation with adjuvants? We wanted to find out so we interviewed Nikolai Petrovsky, research director at Vaxine.

Read on to find out more….

Interview summary

RA: Hello Nikolai, thank you for taking part in this interview. Could you please start by sharing your background and your current focus?

NP: I am research director at an Australian biotech company called Vaxine Pty Ltd. My background is as a clinician, but also I did a PhD in immunology, which is where my interest in vaccines comes from. Vaxine’s current focus is a platform vaccine adjuvant technology we call Advax™, which we’re applying to a wide array of different infectious disease vaccines, including for pandemic and seasonal influenza, hepatitis B, malaria and HIV, but also for more exotic organisms like Japanese encephalitis, West Nile virus and Ebola. We are also looking outside the infectious disease space and applying it to vaccines against allergy and cancer, with good success.

RA: What would you say are the key issues and challenges in the vaccine space right now?

NP: I think the big issue is trying to find the next big vaccine blockbuster. I’m sure a lot of people would tell you funding, because it’s got increasingly more expensive to develop a vaccine. If you look at some of the current blockbuster vaccines including the pneumococcal vaccine, Prevnar, back when they were developed it was often sufficient just to do trials in maybe several hundred subjects before getting that vaccine approved. Nowadays it’s not unusual to be asked to do trials in anything up to 10,000 subjects. And of course, the cost of development has gone up astronomically, so that now we talk about an estimate of around $1 billion to develop a vaccine. It would have been less than a tenth of that maybe 10 or 20 years ago.


“I think the big issue is trying to find the next big vaccine blockbuster.”


We’ve also had a transition in the last 20 years from a focus on childhood vaccines to adult vaccines, and hence there are also big challenges in terms of better understanding the adult immune system. Unfortunately, as people get older their immune responses become more subdued, and it becomes progressively harder to get a response to your vaccine. So when you start trying to target adult diseases with, for instance cancer vaccines, apart from the challenge of making the cancer vaccine work you also have the challenge that the person you are giving this vaccine to may be quite elderly. Therefore even if your vaccine theoretically is the right one it may still fail to work, because that person’s immune system is not as responsive as it might be in a younger person. An adult isn’t just a big kid, they have quite different immune systems, and therefore vaccines need to be designed differently to work well in adults. In particular, adult vaccines need different and more powerful adjuvants to help them to work whereas in children the same adjuvants can be problematic as the child’s immune response overreacts and hence toxicity is the biggest concern. Vaxine has been putting a lot of effort into understanding the basic immunology that’s different between an adult and a child. So for us that’s one of the key challenges moving forward in the adult vaccine space.

RA: What major advances have been seen in vaccines in the recent years?

NP: The last really major technology advance in vaccines would be the polysaccharide conjugate vaccines. The best example is Prevnar, which now has a market of around $4 billion a year, showing just how successful that particular technology has been. The idea that you could take a sugar and by conjugating it to a protein dramatically improve its immunogenicity by providing T-cell help really transformed the vaccine space. What the next big technology breakthrough will be is still hard to say, although I think it might come from the combination of peptide based vaccines, which are extremely quick and easy to make, with the right adjuvant and delivery system, which we hope based on recent promising data will be ours. Another potentially big advance would be to find a way to reliably make effective mucosal vaccines, and again we have some exciting mucosal adjuvants we are currently working on to assist this.


“We’ve also had a transition in the last 20 years from a focus on childhood vaccines to adult vaccines…”


RA: What therapeutic areas look the most promising at the moment for future vaccine development?

NP: Cancer vaccines remain the biggest challenge. The cancer space is enormous, there’s great unmet need. Many cancers are still not curable, and so if we could develop effective cancer vaccines it would have an enormous impact and would also be enormously profitable for the companies developing these vaccines.

Of course there are challenges, and one of those has been that most cancer vaccine trials to date have failed to meet their primary targets. But the potential market size is so large that nothing else compares. Outside of cancer there’s interesting work going on in using vaccines to try and treat chronic diseases, such as hypertension or even nicotine and cocaine addiction. However, there are existing treatments for these conditions and many of them are not immediately life threatening, so even if a vaccine was successfully developed for something like hypertension it would still have a hard time breaking in to the established marketplace against alternative therapies. Whereas in the cancer space a successful vaccine wouldn’t meet any resistance.

RA: What implications does vaccine pricing in the developing world have on pricing in the developed countries?

NP: Very little, I think. We haven’t really seen a situation where very low prices that consumers or governments pay for vaccines in the developing world brings down the price of the same vaccine in the developed world. Maybe the best example of that is the current hepatitis B vaccine, which sells for somewhere around 20-50 cents a dose in the developing world, but still sells for upwards of 30 dollars in the developed world for the same vaccine, a price differential of approximately 100 fold. So the availability of cheap vaccines in the developing world appears to have very little impact on the price of the same vaccines in the developed world.


“…it’s increasingly more expensive to develop a vaccine.”


RA: Finally, where next for vaccine development formulation with adjuvants?

NP: It’s taken a long time to break the dominance that aluminium adjuvants have had on vaccine adjuvants for the last 90 years, and I don’t think alum’s dominance is going to go away any time soon. Alum is very cheap, it’s easily accessible, there are no intellectual property issues, it’s been given to billions of children, and it’s reasonably well tolerated. So it is tough to beat. We and others believe that we have candidate adjuvants that have advantages over alum, but it takes a lot of data to prove this to everyone’s satisfaction, particularly when you are competing against an existing adjuvant that’s so well entrenched as alum. Where we see new adjuvants, such as Advax™ or our new mucosal adjuvants, gaining ground is in indications where alumadjuvants don’t work, such as for T-cell vaccines against the likes of HIV, TB and cancer. This makes it easier because you’re not having to compete head-to-head with alum. That said, we still believe that there are overwhelming reasons why Advax™ being a simple sugar-based polysaccharide is an ideal replacement for alum in all childhood vaccines, but we accept it will be a long haul to generate all the data needed to convince the market and vaccine manufacturers of this fact.

Another area where we know that alum is not strong enough or it doesn’t induce the right type of response is across the range of viral diseases such as RSV, herpes simplex, and CMV. So we’ve got programs targeting these viral diseases with vaccines that include Advax™ adjuvant, and are seeing some great protection data in our models.

RA: Thank you for your time today Nikolai.

NP: It’s been a pleasure.




About the interviewee:

Nikolai Petrovsky is Director of Endocrinology at Flinders Medical Centre with a conjoint position as Professor of Medicine at Flinders University, He is also vice-president and secretary-general of the International Immunomics Society. Active in diabetes, endocrinology and vaccine research, he is the founder of Vaxine, a company funded by the National Institutes of Health to develop novel vaccine technologies. In 2009 Vaxine won the AMP innovation award at the Telstra business awards and Australia’s coolest company award from Australian Anthill magazine. He has developed vaccines against influenza, hepatitis B, sting allergy, malaria, Japanese encephalitis, rabies and HIV, has authored over 90 papers and chapters and is a regular invited speaker at international vaccine conferences.

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