Malaria remains a major challenge in global health and an enormous burden to sub-Saharan Africa in particular, where approximately half of the five million malaria cases occur each year. Despite the remarkable advantages in prevention and treatment, an effective vaccine is still considered the last remaining piece of the puzzle in a successful, long-term fight against this disease. Over the past decade, there has been some extraordinary progress in the area of malaria vaccine research. But we are still running into obstacles. Let’s explore the developments in malaria vaccines, the hurdles to overcome, and the light at the end of the tunnel.
Progress in Malaria Vaccine Development
The RTS, S/AS01 Vaccine
- Summary: The RTS, S/AS01 vaccine or Mosquirix is the first malaria vaccine to receive a positive recommendation from the World Health Organization (WHO). The pharmaceutical company GlaxoSmithKline (GSK) and the PATH Malaria Vaccine Initiative developed the vaccine and tested it in clinical trials.
- Efficacy: RTS, S/AS01 targets the deadliest malaria parasite, Plasmodium falciparum. Results from clinical trials show that it reduces the incidence of malaria cases by almost 40 percent in children under the age of five. This is the highest efficacy observed in any malaria vaccine to date.
- Rollout: Starting in 2021, RTS, S/AS01 will launch pilot programs in Ghana, Kenya, and Malawi, deploying the vaccine at the community level to assess its impact on malaria control and its integration into existing malaria control programs.
New Vaccine Candidates
- PfSPZ Vaccine: This vaccine developed by Sanaria Inc. contains live, attenuated Plasmodium falciparum sporozoites, the forms that infect humans. Results from early trials have demonstrated good efficacy in the prevention of malaria.
- R21/Matrix-M: a malaria vaccine developed by the University of Oxford that showed efficacy rates of up to 77 percent in recent trials, in part thanks to a new class of adjuvant that enhances the immune response called Matrix-M.
Advancements in Vaccine Research
- Genetic engineering: vaccines promise greater efficacy and longer duration Other researchers are looking at genetic modifications to enhance the protective ability of vaccines, such as immunizing against multiple stages of the Plasmodium life cycle.
- Combination vaccines: Efforts are underway to develop combination vaccines with multiple strains of malaria or even other diseases that could build upon the effectiveness of malaria control programs.
Challenges in Malaria Vaccine Development
Efficacy and Durability
- Variable efficacy: Data on the RTS, S/AS01 vaccine indicate that it has some efficacy, but that efficacy differs among populations and across age groups. The vaccine seems to lose efficacy with time, requiring booster doses to maintain protection.
- Durability of Protection: First and foremost, the need for length of immunity is 100 percent. Every malaria vaccine must provide a durable or long-lasting form of protection against a parasite that historically roves between three different life stages or forms (sexual, sporozoite, mammalian blood stages) and which has known multilingual abilities (genetic mutation).
High Production Costs
- Challenges in manufacture: Malaria vaccines, especially those that use live attenuated parasites or complex adjuvants, are expensive to produce. Providing affordable access in low-resource settings is a real challenge.
- Investment and funding: A malaria vaccine would cost a lot to develop and distribute, and it would require financial investment in funding research and clinical trials as well as in mass production.
Distribution and Delivery
- These are the cold chain requirements of RTS, S/AS01, and other malaria vaccines: – storage of vials at 2°C to 8°C and transportation at 2°C to 8°C – lyophilization of the vials and reconstitution of the vaccine before administration – dilution of the reconstituted vaccine with supplied solvent at 20°C to 25°C in a glass vial adapted from a specific supplier meetin’ these requirements – storage of the prepared vaccine and protection against adverse environmental conditions, including light – storage of the prepared vaccine at 2°C to 8°C and transportation at less than 25°C for up to 6 hours – the delivery (administering) of the vaccine itself. To accomplish these steps in resource-poor, remote areas is difficult at best.
- Vaccination infrastructures: successful vaccination programs need to be able to incorporate the infrastructures needed to train staff and deliver the vaccine. In many areas of the world where malaria is rife, such infrastructures are underdeveloped or inadequate.
Resistance and Adaptation
- Immune Escape: The malaria parasites can evolve rapidly, causing a concern that new vaccines may face resistance in the coming years. Surveillance and flexible vaccine design will be important to address these concerns.
- Genetic Diversity: The Plasmodium parasite expresses large amounts of genetic diversity, which may decrease vaccine efficacy. Vaccines need to target conserved antigens to avoid these genetic changes.
The Road to Sustainability
Enhancing Vaccine Research and Development
- Promoting Collaboration: We need increased collaboration among governments, intergovernmental organizations, pharmaceutical companies, and research institutions to accelerate the development of a malaria vaccine. The lack of a malaria vaccine has done far more damage to mankind than any conspiracy theory ever could.
- Sustained investment: Maintaining public and philanthropic funding for malaria vaccine research and development is essential. Investments across the spectrum – including early-, pre-clinical, clinical, and phase-2, as well as scale-up – will help speed progress and new vaccines to the market.
Improving Vaccine Delivery
- Enhance Health Systems: To effectively administer vaccines, we need a robust infrastructure that includes classrooms for training health carers and healthcare workers. Additionally, community health programs and partnerships with local organizations should strengthen distribution systems.
- New Delivery Methods: Inventing new ways to deliver vaccines would overcome logistical barriers and expand access. For instance, needle-free devices or oral vaccines might be useful.
Addressing Equity and Access
- Affordability: It will require ensuring the affordability of malaria vaccines in countries of need through the use of pricing schemes that reduce costs in low-resource settings. One approach is to implement ‘tiered pricing,’ which allows prices to decrease as a larger percentage of the community is vaccinated. Subsidies and international funding mechanisms can play a similar role.
- By mapping out equitable distribution strategies now – such as targeted prioritization of high-risk areas and vulnerable populations – we can ensure that vaccines have the best possible chance of controlling the pandemic in the long term.
Monitoring and Evaluation
- Continued monitoring and evaluation: In order to ensure success, having strong monitoring and evaluation systems to understand vaccine effectiveness and safety will be critical going forward. Moreover, this data will allow for adjustments to vaccination strategies as well as the continued identification of evolving problems. Ultimately, a proactive approach to monitoring will enhance our ability to respond effectively to challenges as they arise.
- Adaptive strategies: flexibility in vaccine policies and strategies is also needed to cope with evolving challenges such as drug-resistant parasites or shifting epidemiology.
The long journey to a sustainable malaria vaccine is characterized as much by pain as it is by promise. Despite the milestones in vaccine development, some of which are nearing licensure, a plurality of hurdles persist to defeat malaria in all of its forms – through vaccine development, efficacy limitations, production challenges, distribution, and resistance. We should face these hurdles with optimism, as malaria vaccines can play a critical role in effectively controlling, and ultimately eradicating, this global scourge of humanity. In addition, fostering collaboration and investment in research will be essential to maximize the impact of these vaccines. Nevertheless, investment in research advances, bolstering health systems, and ensuring equitable access will all be key to effectively and sustainably expanding the reach of malaria vaccines. The road may be long, but it is not insurmountable. If we persevere and commit to innovative solutions, we can realize a malaria-free world.
