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| Malaria vaccine development: no longer a pipe dream? | Malaria vaccine development: no longer a pipe dream? |
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| Saturday, last week, marked the beginning of World Immunisation Week, and Thursday is World Malaria Day. It seems a fitting time to consider these two occasions by posing a seemingly simple, but in fact quite complex, question: what is the role for malaria vaccines in the on-going effort to turn the tide against malaria, an ancient scourge, and ultimately to eradicate this wily parasite? | Saturday, last week, marked the beginning of World Immunisation Week, and Thursday is World Malaria Day. It seems a fitting time to consider these two occasions by posing a seemingly simple, but in fact quite complex, question: what is the role for malaria vaccines in the on-going effort to turn the tide against malaria, an ancient scourge, and ultimately to eradicate this wily parasite? |
| For decades, the answer unfortunately was a quite clear and quite frustrating "none" because, despite compelling scientific evidence that it should be feasible, the Plasmodium parasite outwitted the tools we had at hand. We watched, admittedly with envy, as vaccines against smallpox, polio, measles, tetanus, whooping cough, pneumococcus, and meningococcus, to name a few, gave us the upper hand in preventing if not controlling or eliminating these viral and bacterial diseases. Malaria, however, is caused by a parasite with a complex genome and lifecycle, which has allowed it to pick up innumerable evasion tactics as it co-evolved in humans for a millennia. | For decades, the answer unfortunately was a quite clear and quite frustrating "none" because, despite compelling scientific evidence that it should be feasible, the Plasmodium parasite outwitted the tools we had at hand. We watched, admittedly with envy, as vaccines against smallpox, polio, measles, tetanus, whooping cough, pneumococcus, and meningococcus, to name a few, gave us the upper hand in preventing if not controlling or eliminating these viral and bacterial diseases. Malaria, however, is caused by a parasite with a complex genome and lifecycle, which has allowed it to pick up innumerable evasion tactics as it co-evolved in humans for a millennia. |
| But we have turned a corner. With expansion of long-lasting insecticide-treated bed net use, and deployment of malaria rapid diagnostic tests and artemisinin-combination therapies, it is estimated that more than 274m cases and 1.1 million deaths have been averted between 2001 and 2010. Without a doubt, those are impressive gains; yet the fight is far from over: we need more tools to win this battle — particularly given that these gains are threatened by the economic sustainability of current control efforts, by emerging drug resistance, and by increasing insecticide resistance. | But we have turned a corner. With expansion of long-lasting insecticide-treated bed net use, and deployment of malaria rapid diagnostic tests and artemisinin-combination therapies, it is estimated that more than 274m cases and 1.1 million deaths have been averted between 2001 and 2010. Without a doubt, those are impressive gains; yet the fight is far from over: we need more tools to win this battle — particularly given that these gains are threatened by the economic sustainability of current control efforts, by emerging drug resistance, and by increasing insecticide resistance. |
| So what are the prospects for adding a malaria vaccine? Although pivotal clinical trials are still ongoing, sufficient progress has been made to make relevant the question of the role of a malaria vaccine. As we move closer to the possibility of a licensed vaccine, it is imperative to understand how its role may differ from the roles played by other licensed vaccines, such as those mentioned above. | So what are the prospects for adding a malaria vaccine? Although pivotal clinical trials are still ongoing, sufficient progress has been made to make relevant the question of the role of a malaria vaccine. As we move closer to the possibility of a licensed vaccine, it is imperative to understand how its role may differ from the roles played by other licensed vaccines, such as those mentioned above. |
| To be clear, malaria vaccines will be used in addition to, and not as a substitute for, other control measures. Unlike vaccines for diseases such as polio and smallpox, a malaria vaccine would not and should not be expected to do all of the heavy lifting. It would work with other interventions. In fact, an emerging strategy to eliminate it is to hit it hard and fast by intensifying the assault with every tool we can amass, including a vaccine. | To be clear, malaria vaccines will be used in addition to, and not as a substitute for, other control measures. Unlike vaccines for diseases such as polio and smallpox, a malaria vaccine would not and should not be expected to do all of the heavy lifting. It would work with other interventions. In fact, an emerging strategy to eliminate it is to hit it hard and fast by intensifying the assault with every tool we can amass, including a vaccine. |
| And I am more optimistic than ever about the global malaria vaccine pipeline. | And I am more optimistic than ever about the global malaria vaccine pipeline. |
| The vaccine candidate known as RTS,S/AS01 (pdf) is in the midst of a large phase three clinical trial (pdf), typically one of the final steps before submission to regulatory authorities. Results published so far show that it provides additional protection against clinical and severe malaria for infants and children in settings where bed nets are also widely used. This trial is being conducted — to the highest international standards — exclusively in Africa by resident scientists at 11 sites in seven countries and in partnership with the dedicated team at GlaxoSmithKline, the vaccine candidate's developer. | |
| As we await further data from the RTS,S clinical trial and initial public health impact estimates, researchers at the PATH Malaria Vaccine Initiative (MVI), with our partners, are simultaneously using lessons learned from RTS,S to inform work on next-generation malaria vaccines designed to further improve protection against infection. Using the malaria challenge model, a multitude of vaccine approaches have been and continue to be tested, including revolutionary new approaches to hunt for additional targets to use in new vaccines. | |
| There also are other malaria vaccine approaches in earlier phases of development that target different stages of the parasite's lifecycle. Prospects include vaccines such as transmission-blocking vaccines (TBV) intended to interrupt the transmission of malaria parasites by taking advantage of vulnerabilities that have been identified as the parasites jump from the human host to the mosquito. | |
| Of course there are challenges involved in a disease-fighting strategy that relies on multiple interventions. It requires donors and malaria-endemic countries to fund and implement a wide assortment of tools. Also, while a transmission-blocking vaccine could be crucial to parasite eradication, it will require education of healthcare workers and vaccine recipients to embrace a vaccine that offers no immediate direct benefit to the individual receiving it. The benefit would come later in the form of community-wide immunity leading to fewer infections and fewer deaths, including in the vaccinee. | Of course there are challenges involved in a disease-fighting strategy that relies on multiple interventions. It requires donors and malaria-endemic countries to fund and implement a wide assortment of tools. Also, while a transmission-blocking vaccine could be crucial to parasite eradication, it will require education of healthcare workers and vaccine recipients to embrace a vaccine that offers no immediate direct benefit to the individual receiving it. The benefit would come later in the form of community-wide immunity leading to fewer infections and fewer deaths, including in the vaccinee. |
| Having seen malaria vaccine development progress from a pipe dream to a pipeline, I feel incredibly fortunate to be marking World Immunisation Week and World Malaria Day by contemplating some exciting possibilities while facing the daily challenges of vaccine development. Without a doubt, the gains made to date are impressive; yet the remaining global burden of disease and death remains staggering. Adding a vaccine to the arsenal is more important than ever to win this battle. | Having seen malaria vaccine development progress from a pipe dream to a pipeline, I feel incredibly fortunate to be marking World Immunisation Week and World Malaria Day by contemplating some exciting possibilities while facing the daily challenges of vaccine development. Without a doubt, the gains made to date are impressive; yet the remaining global burden of disease and death remains staggering. Adding a vaccine to the arsenal is more important than ever to win this battle. |
| David Kaslow is director of the PATH Malaria Vaccine Initiative | David Kaslow is director of the PATH Malaria Vaccine Initiative |
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