An Interview with Mark Feinberg

The newly appointed president and chief executive officer of IAVI is no stranger to HIV research, having spent more than 30 years of his varied career battling the virus.

By Kristen Jill Kresge

Mark Feinberg has a broad perspective on vaccine development. He worked in government, serving as a Medical Officer in the Office of AIDS Research at the National Institutes of Health; in academia, as a basic and translational researcher, teacher, clinician, and clinical investigator, including a post as the founder and first Medical Director of the Hope Clinic at the Emory Vaccine Research Center; and for the last 11 years in the pharmaceutical industry, holding various positions at Merck & Co. working on vaccines and infectious disease therapeutics. His most recent position at the company was Chief Public Health and Science Officer for Merck Vaccines.

Beginning September 8, Feinberg added yet another role to his varied career—President and CEO of IAVI. He succeeds Margie McGlynn, another Merck alum who stepped down after four years as IAVI’s head, becoming the organization’s third leader in its nearly 20-year history. Feinberg says the common goal underlying his career is finding a way to “translate science into public health benefit.”

In some ways joining IAVI is like returning home. Feinberg was an MD-PhD student at Stanford University when the first cases of a new and deadly disease that would later become known as AIDS were first reported in New York, Los Angeles, and San Francisco. His thesis research at Stanford with Irv Weissman and Henry Kaplan involved studying the molecular mechanisms of leukemogenesis of human T-lymphotrophic virus (HTLV)—the first human retrovirus to be reported and the only one until HIV was discovered. He then had the opportunity to apply emerging tools of molecular biology to study the role that HIV genes of then unknown function played in the virus life cycle in the laboratory of Robert Gallo, one of the co-discoverers of HIV, at the National Cancer Institute. “I thought that would be an important opportunity,” recalls Feinberg. “I finished my thesis research working on HIV and have been involved in one way or another with the disease since then. That’s more than 30 years, which is remarkable to reflect on.”

Feinberg joined Merck when the company was actively involved in the initiation of the large Phase IIb STEP and Phambili trials, the first HIV efficacy vaccine trials to test a viral-vector based vaccine candidate designed to induce primarily cellular immune responses against the virus. However, his involvement in vaccine research while there extended far beyond HIV. At Merck he was also involved with the development and licensure of several novel vaccines, including those against human papilloma virus (HPV) and rotavirus. Most recently he led the company’s involvement in the public-private partnership to expedite development and testing of a vaccine against Ebola. This candidate, rVSV-ZEBOV, showed great promise in a recent clinical trial in Guinea. Despite these varied experiences, Feinberg says his “scientific heart and mind remained committed to doing something about HIV or at least doing my best to help the overall effort be as successful as it possibly can.”

Nelson Michael, director of the US Military HIV Research Program, has known Feinberg since they were classmates at Stanford in 1979. “I was thrilled to learn that Mark was chosen to lead IAVI,” says Michael, who reflected on how both of their lives and careers have been shaped by the HIV pandemic. “Mark and I have become dedicated HIV vaccine developers. We are now in the enviable position, as longtime friends and colleagues, to slay this dragon side by side.”

As Managing Editor, I caught up with Feinberg three weeks after he joined IAVI to discuss his unique perspectives on HIV vaccine research, his broad experiences, and his vision for the organization.

During your time at Merck you were involved in the development and eventual introduction of several novel vaccines, including those against HPV and rotavirus. What was that experience like?

Being at Merck was really a wonderful opportunity. When I joined there were vaccines in development that addressed diseases of major global health relevance, including rotavirus, which in the absence of a vaccine will kill around 600,000 children each year, the vast majority of them in low-income countries. There was also the vaccine against human papilloma virus, which is in many countries the leading cause of cancer mortality for women. With HPV too, the health impact occurs disproportionately in low-income countries where screening methodologies for cervical cancer and health-care infrastructure aren’t as strong. These vaccines were really very promising technical innovations. It was also really imperative to work to try to make them available in places where the disease impact was greatest and where the benefit of the vaccines would be most pronounced.

At the time there was growing interest in accelerating the availability of vaccines in low-income countries, but there wasn’t a lot of experience with models or success factors that govern introduction of vaccines. I had the opportunity to lead efforts to help accelerate access to these vaccines in low-income countries in partnership with the governments of those countries. We established a number of partnerships, including one with Nicaragua that led to a national introduction of Merck’s rotavirus vaccine RotaTeq in the same year it was licensed in the US and a number of other developed countries. Very quickly after that program was initiated, Nicaragua had the highest rate of rotavirus vaccination of any country in the world, which clearly answered the question about whether you could achieve success in resource-limited settings. Similarly, we established partnerships with the governments of Rwanda and Bhutan early on when Merck’s HPV vaccine Gardasil was first licensed, and those proved to be very successful in getting very high vaccination coverage rates in adolescent females.

In addition to having the opportunity to lead the development and implementation of initiatives to accelerate access to new vaccines in Gavi-eligible countries, I was also fortunate to be provided with the support to lead the development of new partnership models to advance research and development efforts focusing on disease targets that represent major public health concerns, but for which no commercial opportunity exists to recoup a return on the investment in product development. While one example of this is Merck’s Ebola vaccine development program, another was our tremendous partnership with the Wellcome Trust to establish the MSD-Wellcome Trust Hilleman Laboratories—a research and development effort, based in New Delhi, that is specifically focused on developing new and improved vaccines to address diseases that disproportionately affect people living in poverty. All of these examples have reinforced my belief that strategic partnerships between organizations that share a common commitment to public health impact can accomplish remarkable things.

For us, the best way of addressing these questions wasn’t just to speculate about possible programs, but to put concepts to the test and study what the success factors were. Those experiences were really very positive and influential in my thinking.

Were there any shared lessons for HIV that emerged from the experiences with those vaccines?

One important lesson is that understanding the circumstances under which a vaccine would be utilized is critically important, as is doing your best to tailor the product profile of the vaccine to enable it to be successfully implemented in resource-limited settings. Those are issues that need to be considered very early on in the development of a vaccine candidate. They are not something that can be easily retrofitted in the end. You have to think about how you would actually get the vaccine delivered and administered to the person who is going to hopefully benefit from it—that is fundamentally important. This includes all kinds of issues around the product profile, the scale of manufacturing, and the cost of goods. All of those are elements that need to be considered in the course of the development process.

In addition it’s very clear that success in public health only comes through creative partnerships of stakeholders who share a common commitment. When that exists, great things can happen, and if it doesn’t, then success is much harder to realize.

During your tenure at Merck the company was involved in the STEP and Phambili trials, the first to test the concept of a T-cell based vaccine candidate. How would you characterize the results of those trials and how they affected the course of vaccine research?

Merck’s HIV vaccine program was very influential in my decision to go to work there because I had been involved in the early Phase I clinical trials of a number of the vaccine candidates that Merck was exploring and got to see just how committed the scientists and the company were to advancing that program. 
At the time an important research goal was to test the hypothesis about the potential benefits of cell-mediated immunity against HIV as a way of, if not preventing HIV infection, at least enabling an infected person to better control the infection and be less likely to transmit the virus to others, which could help control the spread of the virus in the population.

The STEP and Phambili trials were, at the time, the leading edge of efforts to test this major hypothesis about how you might make an effective HIV vaccine, so when the results came in not only demonstrating a lack of efficacy but also suggesting potential for increased risk of infection, that was deeply disappointing for many people. It was profoundly disappointing for all of us at Merck who worked on the vaccine, as well as the multitude of wonderful partners and volunteers that we worked with to make that trial happen. This also had an impact on the field more broadly with respect to rethinking strategies. While the specific approach tested proved unsuccessful, the overall effort was very informative and valuable. I think it is a reminder for all of us to be as critical of our own ideas as we possibly can be while we seek to do the best science and try to advance scientifically meritorious candidates into well-designed studies that really critically test their potential to deliver the results they’re designed to deliver.

The vaccine field was also influenced by the results of the RV144 trial in Thailand—the first to show any protection against HIV infection. This trial was, and maybe still is somewhat controversial among researchers. What are your thoughts on the outcome of RV144 and the cadre of follow-up studies that are now ongoing or planned?

I was one of the people who was skeptical of the RV144 study and was an author of an opinion piece in Science with many other partners in the HIV vaccine field who expressed concern about that trial. But since then, some very interesting scientific insights and leads have emerged. In particular, the RV144 study provided important clues about what might be a beneficial mechanism of antibody-mediated protection that was previously unappreciated. While additional studies to replicate and extend the RV144 study results are needed, the study investigators have provided the field with important data to frame testable hypotheses. In this regard, the RV144 results will be truly valuable if they can inform new approaches to induce the targeted immune response in the majority of vaccinated individuals, and if this response proves to engender protection from HIV infection in the follow-on study now being pursued. 

The follow-up studies probing potential mechanisms of protection underlying the RV144 results have been very informative and the challenge now for the field overall is to use the insights from these studies to inform future vaccine efforts. This is on one hand a scientific issue but also an issue of how the field organizes itself effectively to test those hypotheses in a rigorous, strategic, and expeditious manner.

Most recently you led Merck’s collaboration to expedite development of an Ebola vaccine candidate. Were there any lessons from that experience that are relevant to HIV?

For me, there were a number of very important lessons from the Ebola vaccine development experience. It was an unprecedented effort, not only in terms of the speed with which the candidate advanced through various stages of clinical trials—progressing from the first-in-human studies to evidence of vaccine efficacy in only 10 months—but also with respect to the number of independent studies done by different partners as part of the development program. It was really impressive to see so many private and public sector partners stepping up to address this pressing public health need and finding ways to align complementary expertise to get the job done in an accelerated way. That was not only what happened with the Merck program but also with other collaborations advancing alternative vaccine candidates. The clinical investigators in the various countries and their partners did a remarkable job launching complicated and high quality clinical trials in a very short period of time.

I saw very clearly just how sincere the interest of private sector partners, including large pharmaceutical companies as well as smaller biotechs, is in addressing important public health needs. It’s very clear that success will only be realized when different stakeholders understand both the potential contributions and constraints that each of the partners face in order to maximize each organization’s ability to contribute. We now need to find ways to foster even more effective multi-sector partnerships to address established public health threats like HIV and to proactively prepare for other infectious disease threats that will emerge in the future. I believe that we can do this, and that we must take the opportunity and responsibility to do so very seriously.

My own view, based on my experience over the past 11 years at Merck, is that the private sector is interested in addressing other global health challenges, including HIV, but there needs to be new models of collaboration developed so that they can partner with public sector entities in creative, more effective ways to maximize progress. I think there’s tremendous opportunity here. With the Ebola crisis you saw how very different organizations from different sectors could find a way to work together when they had a shared commitment, and in that regard, it is the same as the challenge we face with HIV.

Unfortunately, public attention focused on HIV has waned because the pandemic has been around for so long—almost 35 years. Yet more people die each week from AIDS than have died of Ebola in the 2014 outbreak overall. The urgency to enable all HIV-infected people to get effective therapy and to develop effective approaches to protect at-risk individuals so that they don’t become infected remain major imperatives.

After such a broad and varied experience at Merck, why return to HIV, and join IAVI in particular?

While I have worked on a number of diseases and that has been tremendously exciting from a scientific, public health, and personal perspective, my scientific heart and mind remained committed to doing something about HIV, or at least doing my best to help the overall effort be as successful as it possibly can. That was what I focused on through my career in academia and as a physician. That’s why I went to work in the Office of AIDS Research. And that’s why I went to Merck in the first place. Contributing to HIV control and hopefully elimination is really what I’ve always wanted to focus my career on.

My interest in coming to IAVI really grew out of what I have seen working in academia, government, and industry, and that is that I believe there are major opportunities for more effective collaborations between sectors than many people can imagine if they only work in one sector. There is all too often a misunderstanding between the different sectors and I think people don’t fully appreciate the good intentions or the real constraints that exist in each sector. I believe that is a solvable issue, but one that will require innovative approaches to partnership and collaboration. IAVI worked hard under Margie McGlynn’s leadership to become an ever more effective partner and I think there are opportunities to take that to an even more significant level if we understand how we can play the most effective, collaborative, enabling role for the field overall. That to me is a really exciting opportunity. I think there are opportunities to fill gaps, imagine new models of collaboration, and work in close partnership with others to set some powerful precedents in the HIV vaccine field.

My impression, having now been at IAVI for three weeks, is that everything I hoped would be true about the promise of IAVI to be that positive, collaborative presence in the field is true. The people who work here are incredibly dedicated to the goal of HIV vaccine development. They are people who want to be the most effective partners and collaborators that they can be and I feel fortunate to have them as colleagues.

I also feel fortunate to be able to work with really great partners at USAID [United States Agency for International Development], the Bill & Melinda Gates Foundation, the National Institutes of Health, in academic and government laboratories, and a number of other partners including private sector entities and governments. All of these organizations share a common commitment and collectively we have the opportunity to figure out how we can best advance progress across the HIV vaccine field.

So what then is your vision for IAVI and how it can contribute to the goal of developing a preventive HIV vaccine?

Well, in many ways HIV vaccine development does share some of the fundamental aspects of the challenges of Ebola vaccine development. It requires looking for opportunities for different partners to work together in the most collaborative fashion and to have a strategic approach that enables the best science to be done efficiently and then expeditiously translated into informative clinical studies, wherein the most promising candidates can be advanced into efficacy studies in creative ways to get answers as quickly as possible.

When you have a disease like HIV or Ebola, for which either the commercial incentive doesn’t exist or the scientific complexity or risk is too great, it’s really going to depend upon models of collaboration between public and private stakeholders to achieve success. And that means we need to find ways of collaborating effectively and linking different sectors with each other in the most effective ways. And if there are opportunities for organizations like IAVI or others to help facilitate those collaborations, that would be a really important contribution. In addition, we also hope to make valuable contributions to advance and enable basic, translational, and clinical HIV vaccine research—ideally in collaboration with others and in ways that establish platforms for broader research benefit—and to strengthen research capacity in countries heavily impacted by AIDS in innovative and sustainable ways.

Likewise, a lot of great science is taking place in academic and government laboratories, but the people doing the science don’t necessarily have experience in product development so they don’t always have the vision of the end-to-end framework within which successful vaccine programs are developed in private sector entities. Similarly, they don’t often have expertise in bioprocess, scale-up manufacturing, or regulatory issues. That is an area where IAVI has begun to play an important role—enabling the work of others to be translated from concept to hopefully proof of concept. I think that is an important contribution and an area where we can do even more. We can work to achieve the vision of being the facilitators of progress for different partners in the field and can hopefully help connect the dots between different stages of the vaccine development process.

What do you see as the greatest obstacles in HIV vaccine development?

There are many major scientific challenges. The virus establishes persistent lifelong infection that the immune system is unable to clear. No individual is known to have spontaneously eliminated the infection, which makes it fundamentally different from any infection we can now prevent with vaccination. There are remarkably informative studies that describe why HIV is such a difficult virus to contain immunologically in an infected individual, and prevent by vaccination in an uninfected individual. But we need far better understanding of what a truly protective immune response might be and an absolute need to understand how to elicit it in a robust and durable manner in vaccinated individuals.

That being said, there are very promising leads and very interesting ideas emerging from basic research studies. Success will only happen if we take those findings to the next step and ask if we can induce the kinds of immune responses that are hypothesized to be important—whether that is a type of antibody specificity or function, a type of cellular immune response, or some combination of immune protective mechanisms—by vaccination.

However difficult the scientific challenges are, and they are difficult, we also need a way of advancing products through the development continuum in an expeditious, strategic, thoughtful, and informative manner. That is really something that is within our control as a community of researchers working to develop an effective HIV vaccine. We each have to ask ourselves how we can best contribute to the most successful overall scientific HIV vaccine research effort. That is the question IAVI will be addressing when we look to the future: How can IAVI as an organization be the best contributor, facilitator, enabler, and expeditor of progress toward the essential goal of developing an effective HIV vaccine?