MVI discusses what's on the horizon for malaria vaccine development

Ashley Birkett, Director of Pre- and Early-Clinical Development discusses the program's strategy to control malaria and eliminate the disease in the long-term


Q: What is MVI currently working on?

A: RTS,S, the world's most clinically advanced malaria vaccine candidate, is currently undergoing Phase 3 testing, often the last phase of testing prior to licensure. This is a major achievement in the field of malaria vaccine development, and if all goes well, RTS,S will become the first ever vaccine approved for use against a human parasite. However, we realize more must be done if we hope to achieve the long-term goal of eradication. We are eager to build on the progress of RTS,S in order to develop vaccines that will provide even greater levels of protection against this deadly disease. That is why we are moving ahead with a strategy for developing a next-generation vaccine that includes candidates that can block transmission of the parasite as well as blood-stage and multi-antigen approaches.  

Q: Can you explain MVI's strategy?

A: A key part of our strategy is to build on previous vaccines successes and failures, particularly those achieved in human clinical studies. The most notable success to date has been achieved with RTS,S, a pre-erythrocytic candidate that aims to protect against the early stage of Plasmodium falciparum malaria infection. This vaccine candidate was found to be 53 percent effective against clinical disease in Phase 2 trials. We’re now testing it in Phase 3 trials at 11 sites in seven African countries.

At the same time, we're working on approaches that should help us to achieve a 2025 goal set by the malaria community and global health experts. That goal is to develop a product that is at least 80 percent effective against clinical malaria for at least four years.

Q: How do you plan to achieve the goal of an 80 percent effective vaccine by 2025?

A: Our strategy is multi-pronged. We plan to focus heavily on pre-erythrocytic vaccine candidates—those that target the parasite on its journey to the liver or as it matures in an infected person's liver cells. There are also exciting new data in the development of blood-stage vaccines that need to be considered, particularly if they can be effectively combined with a pre-erythrocytic approach. Further, we are widening our focus to include transmission-blocking vaccines and are also pursuing candidates that target the less deadly but more widespread P. vivax malaria.

Q: How have calls for eventual malaria elimination and eradication affected your work?

A: The malaria community's push toward an elimination and eradication focus led us to reevaluate our research and development strategy. The steps we have taken to further diversify our portfolio of vaccine candidates are a direct response to the new focus on the ultimate goal of ridding the world of this deadly disease. However, it is important to note that eradication is a long-term goal, as opposed to a near term one.  Even in the face of an eradication effort, our interactions with experts in the field have emphasized the continued need for us to accelerate the development of vaccines that are highly effective at preventing clinical malaria.  It is therefore of utmost importance that we balance our work in these two critical areas to ensure that we most effectively meet the anticipated needs of those affected most by malaria.    

Q: You mentioned transmission-blocking vaccines. How does this type of vaccine work?

A:  To complete its life cycle and reproduce, the malaria parasite must first infect humans and then be transmitted to and infect mosquitoes, a process that is repeated again and again. Transmission-blocking vaccine candidates typically seek to interrupt the life cycle of the parasite by inducing antibodies that prevent the parasite from maturing in the mosquito after it takes blood from a vaccinated person. Over time, this would reduce the number of infected mosquitoes, leading to fewer people becoming infected, which then leads to further reductions in the numbers of infected mosquitoes and so on until the parasite is eventually wiped out—in other words, eradicated.

Q: How would a transmission-blocking vaccine fit into your overall strategy?

A:  Strictly speaking, a successful transmission-blocking vaccine would not directly protect the individual vaccinated from contracting the disease; it would only impact disease over time by reducing the number of malaria infections in a community. However, we have an increasing interest in multi-stage, multi-antigen vaccines, such that vaccines that prevent disease and transmission could be combined into a single product. Such a combination approach could increase acceptance and therefore deployment and effectiveness of a transmission-blocking vaccine. We believe that a highly effective vaccine that could block the parasite's lifecycle, reduce transmission in endemic areas, as well as provide protection from clinical disease would be a key tool in the global effort to eventually eradicate malaria.