Malaria is one of the most devastating global public health burdens, in particular in sub-Saharan Africa. From the dawn of history, human beings have waged an uphill battle against this devastating disease. Despite remarkable progress in the long battle against malaria, based on antimalarial drugs, bed nets, and insecticides (indoor residual spraying), the disease continues to inflict tremendous human suffering. However, a new class of tools, namely monoclonal antibodies, is allowing us to re-imagine the disease as a target for urgent and innovative strategies. In this article, I discuss how the use of monoclonal antibodies as a new class of medicine to treat and prevent malaria could contribute to transforming global health efforts in a radical new direction.
Understanding Monoclonal Antibodies
Monoclonal antibodies (mAbs) operate on the same principle as those produced by our bodies, but they are created in the lab. A mAb originates from a single immune cell that targets a specific antigen, generating identical copies (or clones) of that cell. Here’s how they work.
- Target Specificity: Researchers raise monoclonal antibodies against specific molecular targets, such as pathogen proteins on the surfaces of pathogens or infected host cells. These antibodies enhance the immune response by specifically targeting these molecular structures.
- Neutralization: They can neutralize the pathogen by binding to it, or they can mark the pathogen for destruction by other parts of the immune system.
- Therapeutic and Preventive Use: Monoclonal antibodies treat infections and serve as prophylactics to prevent diseases. Doctors use these medicines to treat cancers, autoimmune diseases, and various infectious diseases.
Monoclonal Antibodies in the Fight Against Malaria
1. Mechanisms of Action Against Malaria
Monoclonal antibodies offer several mechanisms to combat malaria:
- Prevention of Parasite Invasion: Several monoclonal antibodies bind to parasite molecules on the surface of malaria parasites (Plasmodium) or infected red blood cells, keeping them from invading a new cell.
- Enhanced immune response: The monoclonal antibody attaches to the malaria antigen, thereby increasing the immune system’s capacity to recognize and destroy the parasite.
- Blocking Transmission: some monoclonal antibodies bind to the mosquito stages of the parasite, preventing transmission from human to mosquito.
2. Recent Advances and Clinical Trials
Several promising developments in monoclonal antibody research for malaria include:
- RTS, S/AS01 Vaccine and Monoclonal Antibodies: The RTS, S/AS01 vaccine addresses malaria, but what role could monoclonal antibodies play as complementary tools? Researchers are already investigating these; studies are underway to combine the vaccine with monoclonal antibodies to enhance their longevity of protection.
- Monoclonal Antibodies Directed Against Plasmodium Falciparum Antigens: Clinical trials have demonstrated the efficacy of monoclonal antibodies directed against specific antigens of P falciparum, the most lethal Plasmodium species. These agents have a good therapeutic index and have proven effective in preventing malaria infection as well as parasite load.
- Antibody-Based Therapy: Since those early pre-clinical studies, research has shown promise for the use of antibodies as a potential therapy against malaria – some can cause clearance of malaria infections in pre-clinical models.
Impact and Benefits of Monoclonal Antibodies
1. Potential for Long-Lasting Protection
Another major benefit of monoclonal antibodies is the potential for long-term protection. Whereas vaccines typically require multiple doses or boosters, some monoclonal antibodies offer protection for weeks, months, or even longer with a single administration or periodic infusions.
Example from Clinical Trials: Monoclonal antibodies targeting Plasmodium falciparum provided prolonged protection against malaria in clinical trials, suggesting that they could be easily integrated into existing preventive strategies.
2. Targeted and Specific Treatment
Because the monoclonal antibodies attack only the malaria parasites and not human cells, they also have a better safety profile. Clinical trials of drugs targeting the Pfs230 protein have shown good tolerability, with relatively few side effects.
Testimonial from Dr. María Gomes, Immunologist: Monoclonal antibodies represent a new paradigm in treatment. Their targeted approach offers numerous advantages such as speed, precision, and high efficacy compared to conventional methods. By specifically targeting molecules (antigens) upstream in a pathogen’s life cycle, they minimize collateral damage to the patient’s cells.
3. Complementary to Existing Strategies
Monoclonal antibodies can be added to the arsenal of control measures, alongside existing interventions such as insecticide-treated bed nets and antimalarial drugs. By relying on multiple different tools, we can provide better overall control of malaria and achieve larger declines in incidence.
As Dr Rafael Silva, Malaria Expert ER, told us: ‘If monoclonal antibodies are used adjunctively with the current malaria control measures, there are synergistic effects that improve overall effectiveness and accelerate the road to malaria elimination.
Challenges and Considerations
While monoclonal antibodies hold great promise, several challenges must be addressed:
1. Cost and Accessibility
However, monoclonal antibodies are currently costly to produce and administer, and an important and tricky goal for future endeavors will be to make these treatments affordable and accessible to populations in malaria-endemic areas.
Comment from Amina Mohammed, UN Secretary-General’s Special Adviser on Post-2015 Development Planning, Global Health Advocate: The challenge we have before us is to further reduce the price of monoclonal antibodies to reach the most vulnerable. If we can manage to do this, then we will have made a major contribution to global malaria control.
2. Resistance and Efficacy
As with any therapeutic intervention, monoclonal antibodies could lead to resistance. But if kept in check through continued research on efficacy and ways to adapt strategies to circumvent resistance, the approach holds promise.
‘If these treatments are to remain viable in the long-term, we must monitor and adapt monoclonal antibodies here and other antibodies targeted for human use, or we risk movements in infected populations that lead to resistance,’ says Dr. Samuel Karanja, an infectious disease specialist who was part of the team in South Africa that developed Favipiravir.
3. Regulatory and Logistical Challenges
These therapies require several levels of regulation and logistical coordination – from the development and licensing of monoclonal antibodies to their final distribution. This layer of complexity can slow down efforts to make homes accessible to people who can benefit from them the most.
‘What we don’t have in place is how to get it out,’ says Dr Elina Larsson, Regulatory Expert at Novo Nordisk Foundation. It is the grey area between discovery and clinical use that is revealing how many individuals and pieces of infrastructure need to be in place before a malaria vaccine – such as a monoclonal antibody treatment – can make the jump from lab to real-world patient use. ‘There are still big gaps in the regulatory framework and the way distribution is organized,’ Larsson says. ‘This would be the first step of a long road.’
Future Prospects
In malaria treatment, this approach shows great promise for the long term, and research and development work aims to further enhance the efficacy of antimalarial monoclonal antibodies, render them more affordable, and scale them up. Collaboration between researchers, governments, and international organizations will be critical to make antimalarial monoclonal antibodies a reality.
James Okoro, a friend of mine and an awesomely talented malaria researcher, once said: ‘[w]ith adequate funding and continuing collaboration, we see monoclonal antibodies becoming a game changer in malaria control and cure, a step further towards the ultimate goal of malaria elimination.’
In other words, monoclonal antibodies are an innovative new battlefront in the fight to defeat malaria, and monoclonal antibody approaches could serve as a safe and effective complement to existing malaria control tools, across the malaria elimination continuum. In short, there are sure to be challenges concerning developing and implementing a malaria vaccine based on monoclonal antibodies, but many would argue that the potential benefits of this approach in radically transforming global health efforts toward eliminating malaria makes them worthwhile. As new types of vaccines and approaches are developed to tackle one of the oldest diseases, humanity’s prospects for malaria elimination are sure to be transformed for the better.
