Abstract
Interview by Jenaid Rees, commissioning editor.
Margaret A Liu is best known for her pioneering work in the area of DNA vaccines. A world renowned scientist, Liu was named one of ‘The 50 Most Important Women Scientists’ by Discover magazine in 2002. Liu obtained her M.D. from Harvard Medical School, and has held positions at numerous institutions including Harvard Medical School, Massachusetts Institute of Technology, University of Pennsylvania, UCSF, and the Karolinska Institutet in Stockholm. In her career she has served as Senior Advisor in Vaccinology at the Bill & Melinda Gates Foundation and Executive Vice-Chair of the International Vaccine Institute in Seoul, Korea and worked for companies including Merck, Transgène and Chiron Corporation. Her research achievements have led to her receipt of honorary lectureships, and she has held many board positions throughout her career. Liu currently consults in the fields of vaccines and immunotherapy for companies, universities, and non-governmental and governmental scientific organizations, and is a Foreign Adjunct Professor at the Karolinska Institutet in Stockholm, and an Adjunct Professor at the University of California, San Francisco.
| • | What inspired you to specialize in the field of vaccine development? | ||||
The reason I have spent my career on vaccine development is that it is the convergence of two of my interests: immunology (specifically activation of antigen-specific immune responses); and a desire to benefit the health of people. I’m a physician, and while I loved interacting with people in patient care, it seemed that it would be better to be able to prevent disease in the first place.
| • | You pioneered the development of DNA vaccines, which are now in clinical trials for many human diseases; what do you feel is the most exciting application for this technology? | ||||
Because vaccines are used to prevent diseases caused by infectious agents, one important aspect of vaccines is that logistically, immunizations could be performed to cover whole populations during pre- or interepidemic periods. This avoids the challenges of trying to manufacture and administer vaccines on an emergency basis at the time of an epidemic/pandemic or bioterrorist threat.
I have hopes that a universal influenza vaccine will be developed by targeting conserved epitopes, which could then be useful on a global scale, because the DNA technology has the potential to be used worldwide based on stability, cost, and relatively facile manufacturing processes. This would obviate the need for the annual development, manufacturing, and administration of yearly influenza vaccines, and would mean better coverage in resource-poor countries.
If a DNA vaccine can be made that is efficacious for annual influenza, it is a technology that could be useful to rapidly develop and manufacture vaccines should a pandemic arise due to a strain (such as an H5 avian strain) not covered by the usual influenza vaccine, or for other newly rapidly emerging diseases (such as Ebola). Of course, if DNA vaccines can be developed in a way to work for influenza, the technology will then have demonstrated proof-of-concept for human vaccines, so the technology should be useful for a number of diseases.
Recent data has provided encouragement that DNA vaccines may be useful for other types of diseases and for therapeutic applications including cancer, autoimmune diseases and allergies. A Phase II clinical trial of a DNA vaccine for the immunotherapy of Type 1 diabetes mellitus, developed by Larry Steinman at Stanford has shown positive effects (more insulin and a decrease in the detrimental auto-immune response). This is exciting in terms of being a breakthrough into treating a whole new class of diseases: autoimmune diseases. It opens the door for the use of DNA vaccines for immune therapy, not just prevention of disease due to infectious agents.
| • | In the past, you have worked on HIV vaccines and cancer immunotherapy – both major topics still to be conquered by vaccines – which one do you feel currently has most promise for a vaccine solution? | ||||
The Thai RV144 HIV vaccine trial provided encouragement to all of us working on developing an HIV vaccine, and my colleagues at the Karolinska Institutet have generated quite promising immune responses in their clinical trials using a DNA/MVA prime boost regimen. At the same time, the checkpoint inhibitors have opened a whole new approach to cancer therapy. Now we have the opportunity to attack cancer by providing multiple ways to harness and boost the body’s immune system to battle cancer: via vaccines possibly combined with other immune enhancers, be they cytokines, adjuvants, and/or checkpoint inhibitors.
| • | You consult world-wide for companies; do you think enough money is invested by big pharmaceutical companies in novel vaccine technologies? | ||||
Prophylactic vaccines, immunotherapies that prevent the subsequent development and metastases of cancer (e.g., an HPV vaccine to prevent HPV infection from developing into cancer), and immunizations to treat autoimmune or allergic diseases may be more patient-friendly (i.e., less invasive and requiring limited rather than chronic administration), efficacious, and cost-effective than drugs. So, yes, we need more investments in novel technologies for vaccines and immunotherapies. But investment is needed from many sectors, not simply pharma. More investment in R&D is needed for technologies, but we also need more basic research on pathogens, pathophysiology, and immunity, and more investments in education so that people understand the importance of immunizations and prevention in general.
| • | What do you feel is the future for RNA vaccines and what is the most exciting area of research in the RNA vaccine field currently? | ||||
RNA vaccines provide the opportunity to eliminate the need to deliver DNA into the nucleus, and in doing so, may simplify the process of gene delivery for the production of the antigen. When coupled with self-amplifying approaches, such as replicons, this may increase the potency. Whether RNA (because of stability and cost issues) will become a useful technology, remains to be seen. Of course, although there are licensed veterinary DNA vaccines, it also remains to be seen if DNA vaccines will be a useful technology for human vaccines and immunotherapy!
| • | Vaccines for the developing world have been a focus of your work: do you feel investing into novel vaccine technologies, such as RNA vaccines, can be counterintuitive to the goal of making vaccines more accessible for the developing world? | ||||
While the generic manufacturing of DNA vaccines, and their relative simplicity and stability have been strong attractions for the potential of DNA vaccines, I don’t think one should rule out RNA vaccines as a potential technology for global health based on concerns about the cost or stability of RNA. Recombinant protein vaccines and then polysaccharide-protein conjugate vaccines were once considered too expensive for use in developing countries, as were anti-retroviral drugs for HIV. The key is to find technologies that work (including solving cost and stability challenges), to focus efforts on diseases of developing countries, and to try to ensure that the clinical development is done in parallel in developing and developed countries to eliminate the lag in access for resource-limited countries.
| • | You have in the past been named as one of the 50 most important female scientists; have you ever found your success harder to achieve due to your gender, and do you have any advice for young women aspiring to be scientists? | ||||
I have encountered varied (sometimes-in retrospect- hilarious, sometimes infuriating) challenges due to being a female in science. Mostly, I deal with situations by trying harder and trying to be better. The world was already greatly improved for my generation by the amazing women from earlier eras, but it is discouraging to see still how few women are in senior positions. My advice to young women (and to young men) is to pursue your passion- and that includes not doing what you feel others want you to do to prove yourself. Never undervalue yourself or your accomplishments.
| • | In your eyes, where do you feel the field of vaccines will be in the next 5 years? | ||||
My dream is that society will come to assign more value to prevention as we understand globalization better; that is, we can’t ignore problems that we think belong to some other people or country, and we will realize that the best and affordable solutions may be prevention and immunotherapies that harness the body’s own immune system, rather than simply expensive therapies. But this may not be realistic thinking, and it may take more than 5 years!
Financial & competing interests disclosure
The opinions expressed in this interview are those of the interviewee and do not necessarily reflect the views of Expert Reviews. The interviewee has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.