RSV and Vaccine Hesitancy: Projected Public Health Threat From Current and Emerging Respiratory Viruses

Podcast Transcript

Respiratory Exchange Podcast Series

Release Date: February 14, 2024
Expiration Date: February 13, 2026
Estimated Time of Completion: 30 minutes

RSV and Vaccine Hesitancy: Projected public health threat from current and emerging respiratory viruses

Michaela Gack, PhD

Description

Welcome to a special series by the Respiratory Exchange Addressing the Impact of RSV and Vaccine Hesitancy.  In this series, we explore the efficacy of RSV vaccines and discuss preventive strategies aimed at reducing the occurrence of severe RSV respiratory illness in infants, children and older adults.  

This episode will focus on the Projected public health threat from current and emerging respiratory viruses, where we will explore research on emerging respiratory viruses and vector-borne pathogens. Recognizing the recent advancements in RSV vaccine development while addressing the challenges in RSV epidemiology, vaccination strategies and the importance of education, messaging, and novel approaches in antiviral treatment.

Learning Objectives

• Discuss fundamental aspects of RSV epidemiology, emphasizing risk populations such as infants and the elderly, and explore diverse vaccination strategies tailored for these groups.
• Explain RSV vaccine development and navigate the challenges associated with rapidly mutating viruses, highlighting potential novel approaches.

Target Audience

Geriatricians, infection disease physicians, intensivists, nurse practitioners, nurses, obstetricians/gynecologists, pediatricians, pharmacists, physician assistants, primary care physicians, pulmonologists, and other prescribing and non-prescribing providers. 

Accreditation

In support of improving patient care, Cleveland Clinic Center for Continuing Education is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

Credit Designation 

• American Medical Association (AMA)

Cleveland Clinic Center for Continuing Education designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Participants claiming CME credit from this activity may submit the credit hours to the American Osteopathic Association for Category 2 credit.

• American Nurses Credentialing Center (ANCC)

Cleveland Clinic Center for Continuing Education designates this enduring material for a maximum of 0.50 ANCC contact hours.

• American Academy of PAs (AAPA)

Cleveland Clinic Center for Continuing Education has been authorized by the American Academy of PAs (AAPA) to award AAPA Category 1 CME credit for activities planned in accordance with AAPA CME Criteria. This activity is designated for 0.50 AAPA Category 1 CME credits. PAs should only claim credit commensurate with the extent of their participation.

• Accreditation Council of Pharmacy Education (ACPE)

Cleveland Clinic Center for Continuing Education designates this knowledge-based activity for a maximum of 0.50 hours. Credit will be provided to NABP CPE Monitor within 60 days after the activity completion.  Universal Activity Number List:

Pharmacist UAN: JA0000192-0000-24-296-H06-P

• Certificate of Participation

A certificate of participation will be provided to other health care professionals for requesting credits in accordance with their professional boards and/or associations.

Cleveland Clinic Planning Committee for Addressing the Impact of RSV and Vaccine Hesitancy Series

Cecile Foshee, PhD
Co-Activity Director
Director, Office of Interprofessional Learning

Steven Gordon, MD
Co-Activity Director
Chairman, Infectious Disease Department

Kaitlyn Rivard, PharmD
Co-Activity Director
Department of Pharmacy
Nichole Brown, MSN, RN, CHSE-A, PhD(c )
Nursing Institute

Neal Chaisson, MD
Department of Critical Care Medicine
Department of Pulmonary Medicine 

Frank Esper, MD
Pediatric Infectious Disease
Cleveland Clinic Children’s Hospital

Debra Kangisser, PA-C
Director of Education
Physician Assistant Services 

Aanchal Kapoor, MD, Med
Department of Critical Care Medicine
Department of Pulmonary Medicine

Steven Kawczak, PhD, CHCP, FACEHP
Co-Medical Director, Center for Continuing Education

Neil Mehta, MBBS, MS
Center for Technology-Enhanced
Knowledge and Instruction
Associate Dean of Curricular Affairs, Cleveland Clinic Lerner College of
Medicine 

Anne Vanderbilt, APRN
Senior Director, Advance Nursing Practices
Center for Geriatric Medicine

Hannah Wang, MD
Director, Molecular Microbiology & Virology

Faculty

Michaela Gack, PhD
Scientific Director
Cleveland Clinic Florida Research & Innovation Center

Host

Steven Gordon, MD
Cleveland Clinic Chairman of Infectious Disease Department

Agenda

RSV and Vaccine Hesitancy: Projected public health threat from current and emerging respiratory viruses

Michaela Gack, PhD

Disclosures

In accordance with the Standards for Integrity and Independence issued by the Accreditation Council for Continuing Medical Education (ACCME), The Cleveland Clinic Center for Continuing Education mitigates all relevant conflicts of interest to ensure CME activities are free of commercial bias.

The following faculty have indicated that they may have a relationship, which in the context of their presentation(s), could be perceived as a potential conflict of interest: 

The following faculty have indicated they have no relationship which, in the context of their presentation(s), could be perceived as a potential conflict of interest: Nichole Brown, MSN, BSN, 
Cecile M Foshee, PhD, Michaela Gack, MD, Steven Mark Gordon, MD, Debra Kangisser, PA-C
Aanchal Kapoor, MD, Steven Kawczak, PhD, Neil Mehta, MD, and Anne Vanderbilt, APRN. 

CME Disclaimer

The information in this educational activity is provided for general medical education purposes only and is not meant to substitute for the independent medical judgment of a physician relative to diagnostic and treatment options of a specific patient's medical condition. The viewpoints expressed in this CME activity are those of the authors/faculty. They do not represent an endorsement by The Cleveland Clinic Foundation. In no event will The Cleveland Clinic Foundation be liable for any decision made or action taken in reliance upon the information provided through this CME activity.

HOW TO OBTAIN AMA PRA Category 1 Credits™, ANCC, AAPA, ACPE Contact Hours, OR CERTIFICATE OF PARTICIPATION:

Go to: http://cce.ccf.org/ccecme/process?site_code=main&activity_session_code=EHCE057 to log into myCME and begin the activity evaluation and print your certificate. If you need assistance, contact the CME office at myCME@ccf.org

Acknowledgement: 

The Cleveland Clinic Center for Continuing Education acknowledges an educational grant for support of this activity from ModernaTX, Inc.

Copyright © 2024 The Cleveland Clinic Foundation. All Rights Reserved.

Podcast Transcript

Dr. Raed Dweik:

Hello, and welcome to the Respiratory Exchange Podcast. I'm Raed Dweik, chairman of the Respiratory Institute at Cleveland Clinic. This podcast series of short, digestible episodes is intended for healthcare providers and covers topics related to respiratory health and disease. My colleagues and I will be interviewing experts about timely and timeless topics in the areas of pulmonary, critical care, sleep, infectious disease, and related disciplines. We will share information that will help you take better care of your patients today as well as the patients of tomorrow. I hope you enjoy today's episode.

Dr. Steven Gordon:

Well, hi. And welcome to today's episode of the Respiratory Exchange. I'm your host, Steven Gordon, chairman of the Department of Infectious Diseases here at the Cleveland Clinic. And today I'm very pleased and honored to have friend and colleague, Michaela Gack, who's the scientific director of Florida's Research and Innovation Center. And she's here to join us. So Dr. Gack, welcome to the podcast.

Dr. Michaela Gack:

It's a pleasure to be here. Thanks for having me.

Dr. Steven Gordon:

So today I thought we would take advantage of having a basic scientist and one of the leading innovators here, but to talk, we will focus on RSV and RSV vaccination, again, a new tool in our armamentarium. But also, we want to explore a little bit about a basic science point of view in getting it from someone like, Michaela Gack. So, if I can start, can you just tell us a little bit about your journey, I know you were born in Bavaria, but how did a nice woman from Bavaria end up in Florida?

Dr. Michaela Gack:

Yes, you know, happy to tell you a little bit about my career path. So, I studied molecular medicine in Germany, you just mentioned, I grew up in Germany, and then entered a joint PhD program in Harvard Medical School that was joint between Harvard and my home university in Erlangen, Nuremberg. And that was really molecular virology. So, my training is in molecular virology. I have initially worked on cancer viruses, so very different viruses than RSV, maybe you know that up to 15% of human cancers are caused by viruses. I started out with these types of viruses that are typically causing persistent infections and can cause different kinds of cancer.

But then turned my attention to these emerging viruses that many of us know that can cause acute respiratory infections, such as influenza at the time, and really looking at how these viruses manipulate our immune system. So, they [viruses] really have ways to trick our immune system, get around it, and I was studying early on how the immune system tries to combat these viruses. But, viruses have even smarter ways to get around this immune response.

And I did my post-doctoral fellowship at the University of Southern California. And then actually went back to Harvard to start my own lab, as faculty, stayed there for several years, and then joined the University of Chicago. That was a few years ago. I was then a full professor, and then joined in 2020 Cleveland Clinic right here in Florida, to lead the FRIC, how we lovingly call it, Florida Research and Innovation Center here in Port St. Lucie. And that is very much focused, the center, on infectious disease, immunology, but also getting back to what I studied very early on, how viruses can even cause cancer and in general oncology is another major area here at our center in Florida.

Dr. Steven Gordon:

Well, thank you for sharing that. And we're fortunate, obviously, to have you as a part of the clinic. I want to explore the new and emerging infectious diseases. I like the W.H.O. definition, so it's either a novel pathogen such as SARS-CoV-2 that we've never seen, or existing pathogen that now has that expansion in its geography. The example I might use up here would be Lyme disease in Ohio, which is expanding. So, I'm wondering if you can give us, when we talk about the FRIC, in terms of some of the things, the new and emerging pathogens, that you and your team are focusing on?

Dr. Michaela Gack:

Yes, we focus on the one hand, on emerging viruses that cause acute respiratory infections. That includes, of course, different types of influenza strains. We all know the flu that is a very ubiquitous, very widely spread virus, and can cause really severe disease in certain populations where there are underlying diseases or elderly. But we are also very much focused on vector borne pathogens. And that includes a wide range of mosquito transmitted viruses, Dengue, West Nile virus, and Zika virus, but then also tick-borne pathogens, you mentioned the Lyme disease, our focus is more on tick borne viruses, of which they are really expanding globally, also within the United States, mainly in the northeast. There are currently different viruses such as Heartland virus and other types of these tick-borne viruses. So, these are the two major areas of the emerging viruses, respiratory viruses and influenza. I also would like to mention of course, SARS-Coronavirus-2 and generally Coronavirus is another huge group of emerging viruses, and then the other group are vector-borne, mosquito, or tick-borne viruses.

Dr. Steven Gordon:

Well, thank you for sharing that. I think it's important, too, and as you point out, that we tend to be anthropocentric, that is we only look at humans, so to speak. But, as you have pointed out and as we know, probably two-thirds of the new and emerging infections are zoonosis or, diseases of animals. And of course, we need to know what's going on in animals and animal populations, and again, how that affects so importantly some of the human behaviors that, actually can translate into, downstream into human disease. So that collaboration, which I know that you have in terms of with our veterinarians or knowing about animal health. So, when we saw, for instance, the corvids dying off that was a harbinger, obviously, that there was going to be a problem with West Nile, although many of us didn't know that at the time. So, I wonder if you can comment a little bit about that focus, other than just human.

Dr. Michaela Gack:

Yes, what you said Steve is very correct. So, these are mostly zoonotic viruses. Humans are kind of, I call it, the site hosts. That's not a formal term, but they are widely infecting many different animal species. That's one characteristic of these emerging viruses.

A second one I would like to add is they are typically RNA viruses, so that means the genome is RNA and they have an own enzyme in RNA polymerase to replicate that genome. And that means they also highly mutate. What we have seen with SARS-Coronavirus-2, what we know since decades for influenza virus, they can rapidly mutate as they spread through different species, including humans. So, these are the two basic characteristics of emerging or re-emerging viruses, zoonotic viruses, and they highly mutate because they are RNA viruses harboring in RNA genome.

But as you mentioned, it's so important to not only look at humans. That's only one host of many of these viruses. But really look into also animal species. And there are surveillance programs at many academic institutions or general institutions to look at how these viruses evolve or maybe mutate in animal species; how can they adapt from animals to humans? This is really a strong focus of research in science. What do they need to overcome, to really make the jump, how we call it, from one host species to the other. What kind of adaptations in their genetic material and in their behavior, what do they need to adapt? So it's really important to have insights, not only from scientists studying in humans and human cells, and what we do here typically at our institute, but also, looking at animal species either in the wild or an animal models. It's very important to understand how these viruses behave in their natural host or other species that they infect.

Dr. Steven Gordon:

Thank you. Michaela, I can't help looking at you and talking about this, the importance, of course, of basic science, and the importance, of course, in opening basic science to everyone including women. And as we look at the two recent Nobel Prize in medicine and physiology, as you know, Jennifer Doudna, for her work in CRISPR/Cas and RNA-and of course, this year, Katalin Kariko for her work, modification of the nucleosides, which really set up the platform for the mRNA delivery system for SARS-CoV-2. So, whether you get the Nobel Prize or not, but I'm wondering if you can speak to the importance again in terms of the mentorship, the sponsorship, as well as the coaching, to encourage people, especially young women, to go into science?

Dr. Michaela Gack:

Yes. I think it's more and more we see, obviously, that comes fantastic signs and recognition from women. But still women are often underrepresented in life sciences, unfortunately. But I think what you mentioned, coaching, really encouraging women and everyone, I include everyone, to go into science and really see where your true passion lies in different science fields. This is also besides mentorship and coaching that's very important.

I think the two examples of Nobel laureates you mentioned, these are really women, I think, who followed their true passion in science, and followed that path. And they weren't afraid to come up with completely novel concepts, which a long time ago, not now, because now they won the Nobel Prize, but a long time ago, we know people that didn't really fully buy the concept at the time or appreciate its significance.

And this would be also my advice. Really follow your passion in science, but also don't be afraid to pursue completely novel avenues, even if maybe your peers or some of your peers might not appreciate at the time, at least, the novel concept. Don't get derailed but follow your passion and what you really, truly love and believe in the new concept, what you are proposing. And these are two wonderful examples. I think it's true for both of them. They have really continued and despite maybe early criticism in their concepts, for example, mRNA concept or generally to deliver, these two wonderful examples, I think.

Dr. Steven Gordon:

Well, thank you for sharing that, Michaela. You know as we learn about leadership and phenotypes, you realize that people who do science in novel, obviously, you cannot have a fear of failure. Failure is a part of exploration in this regard. And so, it's not for everybody, probably not for the faint of heart. But I'm sure that you have had many failures, in fact, failures lead to successes in the lab. And I think that's just a wonderful attitude that one needs to have.

Dr. Michaela Gack:

I agree. Scientists shouldn't be afraid of maybe making mistakes or having setbacks. That's often what it's about doing research, meaning if one is doing really cutting edge, novel research, no one knows yet what's the novel concept. What is really the model, the mechanistic details. So, what we very often try is to really propose models of mechanistic understanding.

And these models even I have seen that in my, I say now, relatively young career change over time. Because simply everyone tries to get a step further to, I say now, the truth in biology and this is just the normal process that happens in science as one really goes completely novel avenues that no one has ever really discovered in any of the mechanistic details or concepts. That's a completely normal process in science.

Dr. Steven Gordon:

Well, thank you for sharing that. I want to pivot now to vaccines. You know, as an infectious disease clinician, we'd much rather prevent a disease than treat it. And as you know, a vaccine preventable illness and vaccines are ranked probably amongst the best public health interventions in terms of value going back to Jenner and smallpox vaccine and then moving all the way up to the current 15 vaccines that are recommended for children less than two. Having stated that, we don't have a vaccine for everything, obviously, and we still need basic science, I think, to help us move forward as we talk about protection and providing immunity for animals, but also for humans in this regard.

I'm wondering, as we pivot now to RSV, if you could talk about, there was a discovery, an important discovery made, which set up this subunit vaccine in 2013 in terms of that conformation that preformed conformation RSV-F. I wonder if you can just help us walk that through in terms of how that led to the stage for the vaccines that have been actually approved this year for use?

Dr. Michaela Gack:

This was what you mentioned, in 2013, really getting the structure and molecular understanding. From the prefusion conformation, the different conformation for the subunit vaccine. So, this really was driven by basic research, how can we understand? How can we design it from a molecular aspect, the novel vaccines that are out there now for RSV?

So, everything really started with understanding the structure biology and how to design, in this case, subunit, unit vaccine. We see that very often for most of the vaccine it means basic biology combined from different disciplines, not only virology, chemistry, but also biophysics. Very often a structural analysis of components of the virus that then can help us to effectively design vaccines, be it subunit vaccines or other types of vaccines that are out there.

So, everything in the end is driven by basic research. Sometimes I say, "It sounds so, well, basic." But a much better term is fundamental research. We need to first understand viral components, how they work, what is their structure in order to get to a vaccine. There is, I think, no way around this fundamental, basic research that virologists and other chemists and everyone is working together for this vaccine. 

And what you also mentioned Steve, I think the RSV vaccine is definitely a major breakthrough. But there is still what you mentioned in many, for many viruses, we don't have a vaccine. Just to get back to these mosquito or tick borne viruses, there's practically hardly anything out there that fully protects us, or for most of them, I should say. There are a few out there. But for most of them, for example, Dengue or West Nile virus, there's really no approved and widely approved vaccine available.

But also, another problem is of course for what I mentioned, these viruses mutate rapidly. For example, flu or SARS-Coronavirus-2, even if there is a vaccine it's most of the time ineffective after a short period because the virus unfortunately has already changed. So, these are kind of two major avenues, I think, for these mosquito transmitted viruses but even for the ones we have vaccines, such as some of the respiratory viruses, how can we protect people longer and not just for one year or for a short period? And this is more towards the concept of universal or longer effective or broadly effective vaccines against multiple strains of variants of the virus.

Dr. Steven Gordon:

Oh, well, thank you. You know, as we look at RSV, I wonder if we can talk a little bit about some basic epi [Epidemiology] in terms of setting up the why. If I look at some of those statistics maybe 64 million RSV infections globally, of course that's an estimate because most people are not being tested, maybe half in children. And then, of course, it sets up that platform of those two populations that are really at highest risk for medically attended or severe disease. So obviously, we can talk, we can spread those right into the infants or the babies, especially less than five, and then the elderly, maybe people like myself. But the strategies for vaccination for those two are different. And I wonder if you can walk through the platform, the basics between what we call passive immunization versus active immunization.

Dr. Michaela Gack:

Yeah. As you said there are two principal ways of vaccination. The passive one is really giving already antibodies, very often typically used in infants, for example, from birth to six months, because they simply have no protection. And they also are not very good at making, their own antibodies very effectively so early in life. So that's why we want to immediately protect them by giving them how we call it a passive immunization, which are directly giving them antibodies that have been produced that could immediately work, literally, immediately, from one day to the other after administration and protect the infant.

But then for the elderly, for example typically 60 years and older, who, unfortunately are more prone to a more severe outcomes by a disease outcome by RSV, it's, I say now the classical vaccine, so meaning, you mentioned a subunit vaccine where then, other types, where the body then makes antibodies naturally because it is exposed to an antigen, meaning a component, I say, now, of RSV. And then the natural immune system kicks in and produces these protective antibodies. So, these are principally two ways how to immunize let’s say or protect against RSV for these two vulnerable groups on the one hand, infants, typically less than five years old, and then on the other hand, the elderly, 65 and older.

Dr. Steven Gordon:

Well, thank you, Michaela. Now, the other niche there, is the passive antibody via vertical transmission, so immunizing the mother during that RSV season in the 32-to-36-week range is, I think, now the approval, which is another strategy for passive immunization of the infant. So, I wonder if you could talk to us a little bit about the effectiveness of maternal antibody going to the infant?

Dr. Michaela Gack:

Yeah. This is, of course, very important. And this is again now a new meaning the maternal vaccine, women, pregnant women, being vaccinated and then giving naturally the antibodies to the infant, and thereby causing rapid and immediate, practically, protection after birth. This is the new approved vaccine for pregnant women. It's really to protect against really viral infectious diseases. It's always much harder to wait out if there is an infection and then try to help. Again, these viruses replicate very rapidly.

And it's really much better to have, what you mentioned, protection via the mother, let's say the pregnant woman, the infant, and thereby having a preventative, just in case, if there comes an RSV infection very early on in life, where the infant hardly would be able to make an efficient immune response. This is what you mentioned, thanks for bringing this up this new vaccine, the maternal vaccine, against RSV.

Dr. Steven Gordon:

You know as a clinician, and we're looking, because there's a lot of information coming, and not necessarily a lot of experience, as we're taught, execution is really where we want to get the missed opportunities. You know we learn that from obviously prevention of transmission of HIV in mom for treatment is very important. So, a lot of this is, I think the systems are still being looked at, I understand, too, that there might be shortages of say the antibody in some areas. So that's another reason why you said, that if you can jab the mother that will save the baby a jab potentially, but also the issues about shortages as we're coming up in season. 

You know, the other is of course, attitudes amongst clinicians, because they're the ones that are usually going to be driving the train. And I think part of our goal and role is to educate clinicians on both what we would say, realistically, what the effectiveness is, what the potential side effects are, and what the limitations are. And I think those, coming out of SARS-CoV-2 and COVID-19, I think there was a lot of messaging I think, that we failed, or we failed as a healthcare community, to understand. I look at it as, "Oh my God, there's a vaccine, it can protect, maybe not against infection, but against bad outcomes. Why wouldn't one want to get that?" 

But I've rethought about this in terms of effective messaging for colleagues and for the public. I wonder if you have any thoughts on vaccine hesitancy, vaccine resistance, and just education?

Dr. Michaela Gack:

This is, of course, so important the message. Again, mainly for the public, meaning for the people who we would say are at higher risk, and likely should take the vaccine, but honestly, even to healthcare workers, right, and clinicians, all of them we have seen it with the COVID vaccine, I mean, and even before the COVID vaccine with measles vaccine there has been this already maybe for two decades this trend, Why, do kids need anymore, MMR, or measles vaccine?

I think it's so important to really understand how important it is for the individual. It's also, honestly, going beyond the individual, just to mention that these are infectious diseases. Within a week they can spread from one person to many others. So, it's really about personal protection for, let's say, the infant, or for the kid, or for the adult. But it's so much, really, to understand community spread, even globally, and everything, but mainly for the community. It is really to prevent bigger outbreaks, be it of RSV or measles for example, what we have seen in the past.

So I think what you are saying, education and messaging has become more and more important, that people really hear also the opinion of qualified people who can speak to the protection but also to the potential risk and really make an informed decision of having the vaccine or maybe not having the vaccine.

Dr. Steven Gordon:

You know, it's an interesting point you made, Michaela, because if you look at the guidance for giving vaccine to people over 60 for the RSV it's something called shared decision making and I suspect a lot of clinicians don't quite know what that means, right? In the past you when you look at the guidance for vaccines, you know you order or you give. And so this creates, I think, a new dynamic.

Part of that, my understanding is, of course, there are some things we don't know yet about the RSV in adults in terms of duration. Is it going to be a one season? Is it going to be requiring more? But I think that puts a new onus, but I think a good one on the healthcare provider to become educated about the vaccines that they are going to be recommending or not recommending to the patients. And maybe even the patients also have to do their own education and be their advocates, because they might come up with clinicians that either don't know or are not comfortable with that. And I'm okay with that transparency and empowerment.

Dr. Michaela Gack:

Yeah, I think also in the end, many times, it's a shared decision that really recommended or not, but they could be really dependent on the clinician, also of the patient different outcomes, let's say, if it's really deemed to be needed or maybe not yet needed. And I think also with this vaccine, we really need to learn about, more in terms of protection, how long it would be and again, the populations are very defined which are at higher risk that we know for a long time. But I think now with these newly approved vaccines, I think we will need to see how the hesitancy or hopefully not hesitancy and you know messaging again, very important for this part.

Dr. Steven Gordon:

You know, the other interesting part, I think, and I loved during the COVID, where the W.H.O. came out with a statement that it really should be a universal right that everyone has access to safe, effective. and they were talking about SARS-CoV-2 vaccines, but I think you can put in, underline that for almost all the vaccines that are indicated. And I know that might be a little bit of an aspirational goal, because obviously, as you mentioned, I mean, someone, someone has to pay for that.

But as you point out, the morbidity and the mortality it's just hard as ID clinician not to see the value there. Right? I mean not to go after and set up platforms. As you know, we've eradicated smallpox in my lifetime, and I think Rinderpest pox [cowpox] in animals. But polio remains elusive, although possible. And what I enjoy now is there's challenges, there's other ways of surveillance. I love the wastewater surveillance for viral pathogens. I think, you know, as opposed to depending on people being swabbed, which is a different way. But I'm wondering what your thoughts are about the potential for more effective global eradication or control in the future?

Dr. Michaela Gack:

You mentioned polio. I don't know precisely the year, but I think the original goal was to eradicate it in 2005 or '07, I believe it was, which did not happen. I mean, I think there are certain diseases which, generally we group it into ones which can be eradicated. I mean, we talked about smallpox, polio, and others. But then there are others especially zoonotic ones, I think the scientific community agrees on it, will be very hard to eradicate.

Getting back to what we talked earlier, it's not only the human host. Some of them are very narrow. For example, measles has a very narrow host focus. I mean, that would be in general, if there was really a global vaccine or really widely accepted vaccine and much vaccination it could be possible. But other zoonotic viruses, let's say influenza viruses, or even certain types of Coronaviruses, in my opinion, it’s really very hard to eradicate because they will still always be in the animal host. And they have many animal hosts. And that could be always spillover of new strains like we saw it in 2009 with the swine flu and there have been other obviously from the avian flu in the past.

So that doesn't mean we should give up. There's a whole group of viruses where I think we can aim for eradication. It would need more than a village, I wanted to say really a global effort to do that. And then there's the whole second group of viral agents which I think it will be impossible to eradicate if we're looking for that. Simply too many additional hosts where they could be or will be spillover into the human species.

Dr. Steven Gordon:

Thank you for that perspective. You know, I think it's as you said, new pathogens will continue to emerge. The strategies as we talked about, vaccination, obviously, chemotherapy, antivirals, nonpharmacologic interventions, obviously covering the cough and things, and obviously, reducing one's risk in surveillance of animals, I think it's all very fascinating. And I think as you pointed out it’s not the fortress America or homeland. I mean, you cannot protect yourself from, if there is a problem in North Korea, we need to be there to help from a humanitarian but also from our interest point of view.

And I think we see in many of these outbreaks from the fact that you can be in Rio de Janeiro in the morning and New York in the afternoon, we have our own ways. You know, I know that the airplanes have been looked at as a diaspora, kind of like disease transmitters, potentially. Not to fear anyone, but just to emphasize that it really is a global situation in global protection.

Dr. Michaela Gack:

That is so true, Steve. You know, it's really, since we all extensively travel, anything that happens anywhere around the globe can be in a few days in the United States. Again, that's not really to scare anyone, it's really about having, especially in infectious diseases, have a global mindset in the sense that we want to help, we want to, you know, really support anywhere, because anything, what affects, you know, other countries will also affect us soon here. And I think they are maybe getting back to the preventative or therapeutics for these agents.

I think we have seen with the novel technology's really exciting ways to mitigate, either existing or newly emerging, just getting a faster handle and producing faster vaccines. I think this was an exciting and still is an exciting approach. Just to highlight it there is more and more of the approach and we are working on that in our institute to host based or host targeted therapeutics, which means that we're not directly targeting the virus. But rather, we target, so called host dependency factors in our own human body that support the virus.

I always explain viruses are really tiny, for the most part really tiny creatures having many of them have only 10 genes and some of them have maybe 30 genes, just to put that into perspective of thousands of genes, what we have are tens of thousands. And they use a lot of machinery, and proteins, and enzymes in our own body. I think there is a real push in the scientific community, and also, again, they're already in clinical trials, several agents, to look at host targets, how can we maybe target human factors on which the virus critically relies on for its replication, and infection, and spread? And thereby coming up with novel therapeutics.

That would have a variety of advantages. It could be more broadly acting, many times I explained viruses from one family, they rely on the very same host factors. So potentially you could develop an antiviral that not only protects you against one, I say it now, mosquito borne virus, but multiple ones because they all rely on the same host factor. Another thing is if we target viruses using the traditional approach, targeting the virus directly. These viruses mutate wherever you target them, on that protein or enzyme, what you target.

Over time, unfortunately, many times, they mutate and become resistant. That's sometimes therapeutics antivirals can create a resistancy in the virus. And that would likely not happen if we target host factors or likely not happen. Again, this is really pioneering work. I think we would need to see how the efficacy of such types of therapeutics is but it's just explaining here for the people who are listening, these are new avenues in research which I think well worth pursuing in addition to the more traditional, of course, therapeutic approaches for viruses.

Dr. Steven Gordon:

No, that is fascinating. And Michaela, I want to go back to the beginning, but you know, your role in looking at cancer, and it's interesting, right? Because we look at things like the HPV vaccine and hepatitis B vaccine, it's actually anti-cancer vaccines. And of course, the role of the mRNA platform now in terms of, for certain cancers, is another way of targeting effective chemotherapy through vaccines. So where do you think that is going to be going?

Dr. Michaela Gack:

Yeah. This is also a very exciting area. You know, vaccines for cancer viruses, you mentioned HPV, but they are multiple additional viruses that are either associated with cancer, some of them, of the herpes viruses have been like EBV Epstein-Barr virus, have been associated also with cancer as well with multiple sclerosis, for example recently. So really devastating diseases, cancers, or other chronic diseases.

I think they are a really huge effort to target these viruses, that's of course very different from other cancers where we need to target cancer cells which are our own cells, which in this case, actually, if you think about it, it's you, you have really a unique agent, meaning the viral pathogen, that drives the cancer, that you can target. And thereby create a vaccine against this pathogen. But in the end, it's a cancer vaccine.

If we could get a handle on these, there are only a little bit more than a handful, seven oncogenic viruses. If you get a handle on that, we could control them. It would honestly reduce the overall cancer burden by about 15%, some people estimated 20% of these viral caused cancers. So, it would be hugely significant. And again, they are novel approaches to target, certain types of herpes viruses, some of them are viruses that infect the liver and can cause over time, sometimes cancer.

They are novel approaches to target them and try to prevent their persistency. These are viruses, once infected, they stay in our body for the rest of our life. So how do you prevent this persistent infection and kind of get them vulnerable again and protect us from these.

Dr. Steven Gordon:

Wow. Well, Michaela, this has been wonderful. I appreciate. I'm wondering if I can end on a question in terms of what books are on your nightstand? Or are there any books you're reading now that you would recommend to our audience? It doesn't have to be science.

Dr. Michaela Gack:

I can tell very honestly. It's mainly, scientific journals, not even books. So it's mainly, really, scientific journals that I'm interested in. and beyond books, I mean, I have a five-year daughter there is only a small reading, which is kind of one manuscript. I have no time now for a full book which I can before going to bed, but that’s a good question.

Dr. Steven Gordon:

Wow. Well, thank you so much, Dr. Gack. This has been a great podcast. And to our listeners, thank you very much, and hope to see you on the next podcast. Thank you so much.

Dr. Raed Dweik:

Thank you for listening to this episode of Respiratory Exchange Podcast. For more stories and information from the Cleveland Clinic Respiratory Institute, you can follow me on Twitter @raeddweikmd.