Human Vaccines Project: Discussion with Wayne C. Koff
There’s an urgent public health need to develop more effective and broadly protective vaccines and immunotherapies to combat global diseases that infect and kill millions of people each year. The Human Vaccines Project’s CEO Wayne C. Koff believes that the answers lie within the human immune system. However, no clear roadmap currently exists that deconstructs how our immune system responds to and fights innumerable infectious and non-communicable diseases.
Dr. Wayne C. Koff — Human Vaccines Project
We recently spoke with Dr. Wayne C. Koff, president and CEO of the Human Vaccines Project – a global nonprofit public-private partnership focused on decoding the immune system to improve human health – to gain insights on the learnings from his work in the HIV vaccine field and how he’s applying that knowledge to embark on a new approach that one day will lead to new vaccines and immunotherapies to combat global diseases.
With more than 20 years in HIV vaccine research, Dr. Koff understands the complexities of viruses that invade the human immune system.
Koff has a degree in biology and a PhD in microbiology-immunology. His postdoctoral research included work on the dengue and herpes viruses. Koff was working as a lab professor at MD Anderson Cancer Center when the HIV epidemic broke out, which led to an opportunity at the National Institutes of Health (NIH) as it began its HIV vaccine program. During his tenure at NIH, during the late 1980s to early 1990s, he led the HIV vaccine program for the National Institute of Allergy and Infectious Disease (NIAID), establishing the infrastructure for preclinical and clinical development of candidate HIV vaccines. Prior to founding the Human Vaccines Project, Koff served as chief scientific officer at the International AIDS Vaccine Initiative (IAVI).
Lessons from HIV Vaccine Efforts
Koff explained, “HIV is a complicated virus, which has made it extremely difficult to develop a vaccine. It has unprecedented variability and capacity to infect the cells of the immune system that orchestrate defense against foreign pathogens. As we began trying to develop a vaccine, we had access to the standard tools of vaccine discovery, but one of the things we weren’t able to do was elicit the kinds of immune responses – in this case, the broadly protective antibody and cellular immune responses – that we felt were important for an effective HIV vaccine.
As we delved into that more, we realized we didn’t have the tools to probe the inner workings of the human immune system. As a field, we learned quickly that our preclinical animal models for infectious and non-communicable diseases were less than optimal in predicting human immunity to vaccines, and we didn’t have the biomedical tools that would enable us to fully understand how the immune system worked. Most importantly, we didn’t have the computational abilities to analyze the massive sets of data required to decode the immune system.
In cases like influenza, hepatitis C, and dengue, scientists are working against variable viruses. Instead of needing an antibody response that protects against a single strain of the virus, vaccines against these pathogens need to protect against all the different virus strains. In other cases, there are viruses that actually suppress the immune system itself. HIV is unique in that it’s really like the triple whammy, if you will. It’s hypervariable, immunosuppressive, and there isn’t an ideal animal model to testwhether vaccine candidates will be effective in people.
From Vaccines to Human Immunology
Despite all the years of work and research into developing vaccines, success was elusive. The more Koff and his colleagues learned about HIV and other major diseases, the more they began to realize they did not understand enough about the human immune system This shifted his focus to how the human immune system fights disease, planting the seeds for what would later become the Human Vaccines Project.
The Human Genome Project, a global consortium in the 1990s focused on sequencing the human genome, and was successful after about a decade at a cost of nearly $3 billion, ushering in a new era of biomedical research. Today, a human genome can be sequenced in a day for about $1000. These technological advances in genomics and immune monitoring, together with advances in artificial intelligence and computational science, are now helping Koff and his colleagues at the Human Vaccines Project decipher the components (“parts list”) and mechanisms for how the human immune system works.
Koff notes, “…the common element that kept coming up again and again on the HIV vaccine was that despite our understanding of HIV at the molecular level, we as a field were unable to generate the protective immune responses we were looking for with a vaccine.” Following discussions with colleagues working on other global diseases such as TB, malaria, cancer, autoimmunity and allergy, the limited understanding of the human immune system was impeding progress. Today’s seasonal influenza vaccines protect less than half of people immunized, with less effectiveness in the most vulnerable populations like the elderly. With cancer, while there has been an incredible revolution in immunotherapy ongoing, these therapies are working in less than 25% of cancers, and less than 25% of people who have such cancers; to benefit 80 or 90, or ideally 100 percent of people, we need to understand more about how the immune system fights diseases like cancer.“
As we age, there are certain diseases that we’re all likely be facing – a range of chronic diseases such as Alzheimer’s, heart disease, cancers and metabolic disorders. Koff shared that understanding the common rules of the human immune system would offer areal opportunity to make an impact on these diseases in the immunotherapy, vaccine or the diagnostic spaces. And that all ties back to this unknown “black box” of the human immune system that we are trying to understand. Better vaccines, more effective immunotherapies and access to better diagnostics are necessary against these diseases to really have an impact in terms of mortality and sicknesses.
“To date, we’ve only wiped one disease off the planet. Smallpox was eradicated in the late 1970s. However, we’re on the verge of eliminating polio, and measles might be the next one behind that… The real potential here is to usher in a new era of vaccine and immunotherapy development for a number of major global diseases. This would have a significant impact on human health. That’s really what the Human Vaccines Project is all about.”
How will studying the Human Immune System Help Make Better Vaccines?
Time, Cost & Durability
Koff discussed how advances in our understanding of the immune system will transform vaccinology in terms of the time and cost required for vaccine development, making the process much shorter, cheaper and faster. That’s one of the reasons the Human Vaccines Project was launched – to accelerate development of new and improved vaccines.
One of the flagship programs of the Human Vaccines Project is the Human Immunome Program, which is working to identify all the B-cell receptors and all the T-cell receptors among the world’s population, and then identify the common elements in all people.
Koff explained, “The immune system is varied in individuals on the basis of age, diet, genes, on who your parents are, on where you live, what you’ve been exposed to, what kinds of diseases you’ve had over the course of your life. And yet, evolution is telling us that there are common rules or pathways in all of us for generating protective immune responses.
While vaccines are among the greatest public health advances in history, only a small subset of vaccines like the one for smallpox achieve the ideal: one shot, lifelong protection in everyone. Some require multiple immunizations like hepatitis B, some offer protection for only a few months or years like influenza and pertussis, and many are less effective in vulnerable populations such as infants, the elderly, and the immunocompromised.
- Examples of vaccine durability:
- The measles vaccine is an extremely effective vaccine. It can last for about a decade or so, sometimes even longer
- The yellow fever vaccine can almost last a lifetime
- The small pox vaccine is going to last a lifetime
- The influenza vaccine:
- We have to get it every year because the virus is different every year
- The influenza that actually is out there in the world is different, and
- The antibodies are waning over time and you don’t have enough of the antibodies in the titer
Reduced Number of Vaccinations
Koff elaborated, “The hepatitis B vaccine is a perfect example. The vaccine is licensed as a three-immunization vaccine. It works in about 85 or 90 percent of people after three immunizations. And yet, in about a quarter of those individuals, they actually have generated protective antibody responses after a single immunization.
So, what it is about those individuals? Why are their immune systems able to see the exact same vaccine, and yet give a higher titer after a single shot? If we could understand that, then we could take the hepatitis B vaccine and make it into a single-shot vaccine for everyone. And by extension, a range of other vaccines could be re-engineered to be single shot, rather than multiple shots. This is particularly important for persons living in the developing world, where access to health clinics to receive vaccines is limited.
Long Term Goals
Koff anticipated that it likely it will take at least a decade to decode the human immune system. He envisions continued technological advancements which will accelerate genomic sequencing and immune monitoring and even more advances in computational biology for analysis of the unprecedented scale of data to be generated by the Project. If successful, the Human Vaccines Project could revolutionize our understanding of the human immune system and usher in a new era of global health.
Outside of vaccines, Koff also talked about the broader implications for the work of the Human Vaccines Project in the diagnostic and immunotherapy areas.
Koff explained, “In the diagnostic arena, for a number of diseases, we don’t have early biomarkers in advance of the symptoms. This is particularly true of autoimmune diseases such as MS, diabetes and inflammatory bowel disease, but also true of neurodegenerative diseases such as Alzheimer’s, Parkinson’s and others. By creating a catalog of immune receptors, one will have a framework for then comparing the immune systems of healthy individuals with those at high risk for such diseases. We envision in some cases that the Project will be able to determine new biomarkers for such diseases, potentially enabling disease prevention or slowing the onset of disease.
Koff shared that immunotherapy is very much revolutionizing how scientists look at cancer and potentially autoimmune diseases, even though it currently only works in a subset of individuals and a subset of the cancers.
“Until now, almost all cancer vaccines have basically failed. And most immunotherapies have failed until the last decade or so, when it was realized that some cancers have designed a way to put a “brake” on the human immune system. A cancer cell can fool the immune system into not attacking it. However, investigators have now identified antibodies known as these checkpoint inhibitors that can unlock these brakes, enabling immunotherapy to be successful. In some cancers and in some individuals, there have been unbelievable results in a very positive way. But at the same time, the majority of people aren’t seeing that same benefit.”
Therefore, if scientists can understand why only some cancer patients’ immune systems can identify and kill a tumor, they can work towards enabling a larger percentage of people to benefit from treatment. At this year’s annual Scientific Steering Committee of the Project, all the Project’s academic, corporate, government and NGO partners came together for a session dedicated to how the Project might plan studies aimed at better understanding how the human immune system fights cancers, with the long term goal of accelerating improvements in cancer immunotherapy.
Recent Achievements and Current Focus
Koff highlighted the recent progress of the Project, and its future direction. Since leaving the International AIDS Vaccine Initiative in 2016, he noted that the Project is completing its “catalytic period” of organizational development where academic scientific hubs were established, corporate, government, and NGO partnerships were executed, an internationally recognized Board of Directors and Scientific Steering Committee set up, and the Project’s two major scientific programs launched.
The two major scientific programs launched by the Project in 2017 include the Human Immunome Program, focused on deciphering the components and common elements of the human immune system, and the Rules of Immunity Program, focused on the integration of the components to understand the key principles of protective immunity applicable to developing one-shot vaccines that confer life-long protection in everyone. Initial data from these programs has recently been publicly presented and should be published in 2018.
The Project recently established a new program, the Universal Influenza Vaccine Initiative, which will address the major scientific obstacles that are impeding the development of a universal flu vaccine, and launched a fundraising campaign to raise the next $100 million to complete a series of pilot studies in each of these programs to determine how age, gender, ethnicity and geography impact the human immune response to vaccines. Using the most comprehensive array of technologies ever brought together for the study of human immunity, the Project aims to begin deciphering the correlates and mechanisms of protective immunity, and apply these principles to accelerating development of next generation vaccines.
Michelson Prizes for Human Immunology and Vaccine Research
The Michelson Medical Research Foundation (MMRF) has funded a $20 million initiative with the Human Vaccines Project to support young investigators applying innovative research concepts and leveraging disruptive technologies to defeat major global diseases by advancing the development of future vaccines and therapies. You can read more about the three inaugural 2018 winners here.
Michelson Vaccine Development Conference Video
2018 Annual Conference on the Future of Vaccine Development — Session #01: Introduction [2018-06-27. Ian Gust, Steve Kay, Wayne Koff, Gary K. Michelson. HVP/USC] [Transcript]
- (Featured Image) Wayne Koff believes India is an attractive destination for vaccine development from We’re in a renaissance period for the HIV vaccine: Wayne Koff [2015-03-30. Nikita Mehta. livemint]
- (Illustration #1) Wayne Koff, PhD, President and CEO of the Human Vaccines Project from Scientists find new antibodies to help in HIV vaccine quest [2011-08-17. Meredith Mazzotta. ScienceSpeaksBlog.org]
- (Illustration #2) Human T cell (blue) under attack by HIV (yellow) from Human Immunodeficiency Virus (HIV) [National Center for Biotechnology Information, U.S. National Library of Medicine]
- (Illustration #3) Herpes virus and antibodies from iLexx/Envato Elements
- (Illustration #4) Syringe from stevanovicigor/Envato Elements
- (Illustration #5) Hepatitis B Blood Virus from Pixel Squid 360/Envato Elements
- (Illustration #6) Syringes from eAlisa/Envato Elements