31 Dec 2014

Rick King, PhD, joined the PATH Malaria Vaccine Initiative (MVI) in May 2014 as director of research and development (R&D) and head of the transmission-blocking vaccine (TBV) priority area, one of two areas of focus for MVI.

Prior to joining MVI, Rick served as Vice President of Vaccine Design for the International AIDS Vaccine Initiative (IAVI), leading IAVI's global efforts to design and prioritize novel AIDS vaccine strategies. Rick also previously served as Senior Vice President of Research at GenVec, Inc., managing the company's efforts in the identification, selection, and advancement of products for cancer, ocular, and infectious disease applications.

We recently sat down with Rick to learn about what motivates him to work in vaccine development.

What do you like most about your work as MVI's R&D director?

I have a fascination with biological systems and with intervening in those systems to generate a therapeutic or intervention of some kind—diagnostic or preventative. It's an exciting challenge and one that I find intriguing to be part of. There's also a little bit of fascination with engineering problems: My dad was an engineer who worked on the Apollo (space) program, and I think engineers are fascinated by machines. I'm similarly fascinated by how biological systems work and how to make them change. To do that in an environment where you're really trying to address an enormous outstanding human need combines these two things that are very rewarding.

How did you become interested in vaccine development?

I'd been involved in very basic biochemical and molecular biological research for a long time—since the 1980s—and it was quite early in my career when I became interested in applications related to these areas.

Could you expand on your interest in developing malaria vaccines?

I think the thing that is really exciting about malaria vaccines now is the prospect of success. We have evidence in human clinical trials that malaria vaccines can be effective. We have data that we can follow to try to improve the activity of those vaccines. We know a lot about the molecular biology of the parasite to target those vaccines, and we know increasingly more about how to apply those vaccines in the field. So I think there's a great opportunity to make a difference in a relatively short amount of time, even though it will still take years. The progress is tangible so I think that's exciting, and of course, malaria is an enormous medical problem that needs to be dealt with.

What are some of the major challenges that you face as MVI's director of R&D?

The biggest challenge is the disease itself. As with all of the remaining medical challenges that we face, the complexity of this problem is substantial and there are things that we just don't understand yet about how to do what we want to do. For malaria, one of the fundamental challenges is a deep understanding about how a vaccine actually functions at the detailed molecular level. For example, how do antibodies block the sporozoite form of the malaria parasite from infecting a liver following its injection into a person by the mosquito? We don't really understand that. We understand that it can happen, but we don't understand the basic details of how it occurs, and that lack of understanding is limiting our progress to some extent.

What challenges do malaria vaccine developers face?

There are many other outstanding questions, such as: Do we have the right vaccine targets? How do we best deliver them? Can we control the immune system?

The disease itself and the complexity of generating a vaccine against a hard target like this disease is by far the biggest challenge and the one that is the most interesting and rewarding to think about.

Why are transmission-blocking vaccines and anti-infection vaccines priority areas at MVI?

We have to find ways of attacking the life cycle of the malaria parasite at places where the parasite hasn't had the benefit of evolution to evade the human immune system. What I mean by that is, all diseases of people—and other animals as well—have figured out a way to survive in the face of the immune system, and malaria is no different. The malaria parasite has figured out how to conduct its life cycle in a human while an immune response is going on, where our bodies are doing their best to shove the organism out. And the parasite does this in very effective fashion. But during the period when the disease is occurring, the immune system is also raging against the parasite, so there's a bit of a race during that disease phase.

The malaria parasite has figured out two places where it can evade the human immune system almost completely. One is during the infection phase, when the parasite needs to be able to get from the mosquito into our livers without the immune system interfering in that process. In that phase, it uses speed: it just gets there very quickly, and there's not much time for the immune system to be ready and adapt to that process. We're targeting that phase with the development of anti-infection vaccines, or AIVs.

The other place that the malaria parasite can undergo a portion of its life cycle completely outside of our immune system is in the mosquito, and this is where MVI's other priority area, transmission-blocking vaccines, comes in. When the parasite goes to the mosquito, the human immune system is not involved and the parasite can do what it needs to do, which is undergo sexual reproduction and then generation of the infective stage for humans—the sporozoites. That process is occurring outside the surveillance of the human immune system. If we could figure out how to attack that portion of the parasite's life cycle, it has no natural mechanisms to defend itself.

So that's what we're trying to do: we're trying to teach the immune system something that it doesn't normally learn during a malaria infection and trying to attack the parasite at that vulnerable point. The goal would be to not affect any individual who is affected by malaria transmission itself, but to block the cycle of transmission.

Have there been any recent advancements relating to transmission-blocking vaccines?

The exciting thing about transmission-blocking vaccines—or TBVs—is that in the last couple of years, they have been in clinical trials, and we are beginning to understand how existing TBV vaccine candidates perform in those clinical trials. Those trials give us an opportunity to assess how far we have to go. I don't think we're where we need to be. We're not there yet, but by testing the approach in people, we really get the best information about how far along the path we have come and how far we still need to go.