Anthony Fauci, MD, on Vaccines for Emerging Infectious Diseases


In this podcast, Anthony S. Fauci, MD, discusses the need for rapid, efficient development of vaccines for emerging infectious diseases, the 3-prong approach for staying ahead of the curve, and more.

Anthony S. Fauci, MD, is the director of the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, in Bethesda, Maryland.

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Dr Anthony Fauci: My name is Dr Anthony Fauci and I'm the director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.

In this presentation, I will be speaking about my lecture at IDWeek on October the 6th of 2019. The title of the lecture will be "Vaccines for Emerging Infectious Diseases Threats -- From Science to Implementation." I'm going to talk about the concept of emerging and re-emerging infectious diseases.

Which over the last few decades of which I have been in my current position, I've had to deal with the onset of brand new infectious diseases like HIV, SARS, and the re-emergence of old infectious diseases on the new situations.

The point that I'm going to make is that in the 21st century now, clearly one of the major countermeasures that we have to address emerging and re-emerging infectious diseases is the importance of the development -- rapidly and efficiently -- of vaccines against these pathogens.

The 21st century approach is a bit different than what we've done in the past. I've divided it up into three separate components, what I call the Priority Pathogen Approach. In other words, to anticipate what a particular pathogen might be and to try and get a jump start on countermeasures, particularly vaccines.

We first got into this following the 2001 anthrax attacks, following the 9/11 attacks on our country when anthrax spores were sent through the mail, which triggered a biodefense effort to protect us and develop countermeasures against known select agents like smallpox, anthrax, botulism, plague, and Ebola. In other words, to pre-select a pathogen and to try and develop countermeasures. The WHO also has their own blueprint of priority diseases which they developed in 2018. And an organization called the Coalition for Epidemic Preparedness Innovations, or CEPI, also has priority pathogens. That's one approach.

The next approach is what I call the platform development approach, in which you perfect various platform technologies. Very different from the tried-and-true older, classical ways of growing a particular pathogen like a virus and either inactivating it or attenuating it.

Right now, we have platform technology such as DNA and RNA. Viral vectors with inserted genes that express the proteins of particular pathogens. We have recombinant proteins. We have nanoparticles, virus-like particles, and also there is adjuvant. The perfection of these are things that would give us a head start when we have to respond rapidly.

The third approach of the 20th century approach towards vaccine development for emerging infectious disease is what we call the Prototype Pathogen Approach. You build on prior experiences with pathogens that belong in the same broad genus family or species of a particular pathogen.

For example, take the flaviviruses. We have a number of flavivirus vaccines. We've had experience with flaviviruses, like Japanese encephalitis, dengue, yellow fever. When West Nile and Zika came along, we used our knowledge and experience of the basic virology, the assays for preclinical and clinical setting, animal models, optimal platforms, immune correlates; all of which had some degree of similarity with the particular prior experience that we had with viruses that belong in the same genus or the same family.

So, let me give you some examples of vaccines that are currently being developed and addressed for emerging infectious diseases that call upon these 3 components that I was mentioning. And again, just to remind you of what we were talking about. It's priority pathogen, using known platforms and prototype pathogens.

Let's take Zika, the experience of which we had beginning in 2015. That is both a prototype pathogen and the use of novel platform technologies because Zika is a flavivirus. We used our experience with Japanese encephalitis and yellow fever and dengue to get us to understand very rapidly what we needed to know about Zika.

We also used interesting platform technologies such as a DNA vaccine approach. The first time we used a DNA vaccine was in response to SARS. It took us 20 months from the time of the sequence selection of that virus to the time we got it into a first human injection in a phase one trial. The next time we used it was with the H5N1 bird flu in 2005. We got it down to 11 months from sequence selection to phase one. The H1N1 pandemic of 2009, we got it down to four months.

Finally, when got to Zika, from the time we got the sequence of Zika, to the time we actually put it in the phase one trial, was less than 4 months. It was actually 3.25 months. So, the experience of that platform technology allowed us to respond rapidly. And now we have a phase 2B clinical trial ongoing in South America and the Caribbean.

Another emerging pathogen is Ebola. Again, it's a priority pathogen because we had already pre-selected that in our biodefense program. This put us way ahead of the curve when we had to respond to the outbreak first in West Africa in 2014 to 2016, and now the ongoing current outbreak in the Democratic Republic of the Congo. So, the priority pathogen approach put us in good stead.

We also used modern platform technology for vaccines. The vaccines that are being used right now that has been shown to be successful in Guinea getting is the VSV vaccine design, in which we take the VSV and insert the gene of the glycoprotein of Ebola, which led to a successful vaccine.

There's also a recombinant adno 26 Ebola plus an MVA boost that actually is another candidate vaccine for Ebola. Another example of using these types of pre-selection. Influenza also is a priority pathogen because we have continual seasonal experience with flu. And we also are occasionally confronted with a pandemic. Again, platform technologies such as the most recent ones that we've been developing such as viral vectors, viral-like particles, and in fact, I could mention that a nanoparticle approach is being used to develop a universal flu vaccine, where the stem component of the hemagglutinin is being essentially put on a self-assembling nanoparticle that has already been in phase one trial for group one influenzas. We already are well on the way to the multiple steps towards a universal influenza vaccine.

Now, despite the advantages of this three pillar approach of using Priority Pathogens, Platform Technologies, and Prototype Pathogens, we have a number of challenges that still remain. For example, well known diseases in which there are no effective vaccines such as with malaria, tuberculosis, and HIV, we had to take a different type of approach.

With HIV, we empirically tested a number of vaccines until we finally had a positive efficacy signal, modest though it might be, with a candidate that was tested in Thailand. It was a poxvirus vector, followed by a boost of a protein. Using that modest success, we have built on that by increasing the strength, breadth and durability of the response by developing and identifying immune correlates.

In that regard, there are a number of vaccine trials that use that model of the Thai trial, which we refer to as RV 144, in multiple trials using that same model in Sub-Saharan Africa in a recent one that will be not only in North and South America, but also in Europe.

Another approach, which is really a quite sophisticated approach, is what we call Structure-Based Immunogen Design. Structure-Based Immunogen Design means that we actually developed an immunogen to conform to the right structure to engage B cell lineages to be able to induce broadly neutralizing antibodies for HIV. At the same time as we're pursuing the empiric approach that was modestly successful in the Thai trial, we're now developing a number of immunogens specifically geared at inducing broadly neutralizing antibodies. There are a number of approaches that are right now in early preclinical and phase one trial.

What we learned from that Structure-Based Vaccine Design that you could apply it to other pathogens. For example, the newer approaches towards the development of a respiratory syncytial virus vaccine calls upon the Structure-Based Vaccine Design approach that we utilized with HIV to develop a pre-fusion protein as the immunogen for what looks like a very promising respiratory syncytial virus vaccine.

These are just some of the vaccines that are currently being developed with these newest technologies for emerging and re-emerging infectious diseases.

As far as a key take-home message from my session, it's that we have always had emerging infectious diseases. We have them currently and we will continue to have them in the future. One of the best countermeasures against these is a good vaccine to protect individuals against the spread of these emerging infections. Modern 21st century technologies and new novel approaches that I've described in my talk clearly are going to be at the forefront of a successful vaccine approach to emerging and re-emerging infectious diseases.

Thank you very much for listening today. For more information about my session and additional resources, please click the links below.