Malaria remains one of the most difficult global health problems. In 2020, there were an estimated 241 million cases of malaria worldwide, and approximately 627,000 people died from the disease. Consequently, this burden falls most heavily on sub-Saharan Africa, where nearly 95 percent of the global deaths from malaria occur. Over the past two decades, however, incredible progress has been made in controlling and lowering the morbidity and mortality associated with this disease. This progress has been achieved through the use of insecticide-treated nets (ITNs), indoor residual spraying (IRS), and antimalarial drugs. Nevertheless, these solutions are far from complete. Furthermore, the development and use of monoclonal antibodies (mAbs) represent a novel approach to malaria control that has the potential to lead to a game-changing solution for the universal control and elimination of this devastating disease.
Understanding Monoclonal Antibodies
Made in a lab, monoclonal antibodies bind to a particular target. They are generated by a process that grows identical copies of a single antibody-generating cell, hence the name mono (Latin for ‘one’) or identical ‘clones’. This means that a monoclonal antibody will be uniform, that is, consisting of a homogenized and highly specific set of antibodies. We have been using monoclonal antibodies to treat human diseases for decades cancer, autoimmune disease, and now, finally, infectious diseases (including malaria).
Mechanism of Action in Malaria
Reducing transmission or early treatment of malaria can cut down transmission and prevent severe disease and death. Monoclonal antibodies actively inhibit specific components of the parasite or the host’s response to parasites. They block sporozoites from entering target liver cells, preventing initial infection. These antibodies also stop parasites from emerging from liver cells after weeks or months of incubation, halting their entry into the bloodstream. Additionally, neutralizing antibodies physically disable infected red blood cells, prompting their removal by the spleen. Some antibodies even prevent the parasites from attaching to red blood cells altogether, further disrupting the infection process.
- Inhibiting Infection by Parasite Antigens: Neutralising antigen-bound monoclonal antibody to the malaria parasite (Plasmodium spp.) interferes with binding to red blood cells, preventing infection and inhibiting the ability of the parasite to replicate and cause disease.
- Antibodies That Enhance Immune Response: Some monoclonal antibodies can enhance the host’s immune response against Plasmodium. Upon binding receptor molecules, they can enhance the body’s killing activity and nurture its response against the invading parasite.
- Objective: Disrupt Transmission — For each lifecycle stage, there’s another potential target Monoclonal antibodies can be designed to disable the mosquito vector’s ability to transmit Plasmodium. For example, antibodies could target the surface molecules of the parasite that are crucial to its development in the mosquito.
Current Developments in Monoclonal Antibody Research
Several monoclonal antibody candidates are under development or in clinical trials:
1. Antibody-Based Vaccines:
Other malaria vaccines, based on monoclonal antibodies, can be used to immunize individuals against Malaria by eliciting an antibody response that, in turn, will protect the individual against the parasite.
Case Study: RTS, S/AS01 Vaccine: (The RTS, S/AS01 (Mosquirix®) vaccine) Antigen-based vaccines, such as the RTS, S/AS01 (Mosquirix®) vaccine, a 3D-structured virus-like particle displaying a C-terminal portion of the Plasmodium falciparum circumsporozoite (c) protein (PfCSP), have proven partially efficacious in protection against malaria. Researchers have approved further work to determine whether monoclonal antibodies can enhance the vaccine, improving both its efficacy and duration of protection.
2. Therapeutic Monoclonal Antibodies:
Therapeutic monoclonal antibodies will target either particular stages in the parasite’s lifecycle to treat existing infections or potentiate the host’s immune response to the infection.
Case Study: AETIOLOGY and PATHOGENESIS OF MALARIA (APAM) Project: The APAM project explores a new approach for malaria therapy by targeting the liver stage of the Plasmodium parasite using monoclonal antibodies.
3. Transmission-Blocking Monoclonal Antibodies:
These antibodies act against the malaria parasite residing in the mosquito vector, preventing the parasite from getting into the human host. It targets the parasite itself, without acting on the mosquito vector. This type of intervention reduces the burden of infection in the population by targeting the pathogen at one stage in its lifecycle.
Case study: Transmission-Blocking Antibodies: Antibodies, particularly known as monoclonal antibodies being developed, bind to an antigen present on the surface of the malaria parasite in the mosquito vector. This binding will reduce the ability of the parasite to develop and be transmitted.
Advantages of Monoclonal Antibodies in Malaria Control
The use of monoclonal antibodies offers several advantages over traditional malaria control methods:
1. Specificity and Precision:
Monoclonal antibodies tend to be highly specific. They can be designed to target just the right type of molecule – specifically, antigens linked with the malaria parasite. Such specificity lowers the risk of adverse off-target events (a major issue for older antimalarial drugs) and increases the odds of prompt and effective treatment or prevention.
2. Long-Lasting Protection:
Unlike a vaccine using a dead bacterium or virus, antibody-based treatments can also provide sustained protection through injections that regularly maintain high levels of the targeted protective antibodies in your blood over extended periods. In some cases, this could help reduce the incidence and improve the public health outcomes for malaria and other diseases with a complex epidemiology.
3. Enhanced Immunity:
Monoclonal antibodies help to boost the immune system’s response to the malaria parasite by lending a helping hand to the defenses.
4. Potential for Combination Therapies:
Many of these agents, including monoclonal antibodies, can be added to other malaria control approaches, such as antimalarial drugs and vaccines, to increase their overall efficacy as a treatment and/or prevention strategy.
Challenges and Limitations
However, alongside their promise, there are significant hurdles and caveats to the use of monoclonal antibodies for malaria control:
1. Cost and Accessibility:
Monoclonal antibodies are expensive to produce and might not be accessible in all populations, especially in low-resource settings. Lowering the production costs and boosting distribution will be the key to their use in the future.
2. Development and Production Time:
It could take many months to develop and produce the monoclonal antibodies, in addition to pre-clinical and clinical research and trials to determine their safety and efficacy with certainty. Needless to say, we urgently need to speed up the entire process.
3. Resistance Development:
As with all therapeutics, it is possible that the malaria parasite can develop resistance to monoclonal antibodies, necessitating continual surveillance and adjustment of strategies to thwart these scenarios.
4. Integration with Existing Programs:
Combining them with existing malaria control programs and coordinating with other interventions will be vital to the greatest impact.
Future Directions and Potential
There are some exciting prospects for monoclonal antibodies in malaria control: several avenues of development and study are open:
1. Enhanced Research and Development:
Further investment in research and development is necessary to develop new and improved monoclonal antibodies, to optimize their production, and to further examine the potential of monoclonal antibodies in combination with other interventions.
2. Public-Private Partnerships:
Pairing the public and private sectors seems likely to help us solve challenges of cost, production, and distribution so that people who need the drugs can get them, including through the development of low-cost, properly administered treatments such as monoclonal antibodies.
3. Global Health Initiatives:
Using monoclonal antibodies for global malaria control can make these interventions more effective and increase our chances of global eradication. Integrating them into programs like the World Health Organization’s (WHO) Global Technical Strategy for Malaria would move us closer to our long-term goal.
4. Monitoring and Evaluation:
Ring-screen or other robust monitoring and evaluation systems will be necessary to evaluate the efficacy of the monoclonal antibodies, to understand how well they work and which use them, and to measure their effect on malaria control and adjust accordingly.
Monoclonal antibody-based interventions represent an innovative and powerful new approach Against malaria that if developed offers the promise of specific and perhaps long-lasting, cost-effective, and powerful means of intervention. Of course, technical hurdles remain, but the persistent exploration and refinement of monoclonal antibody research offers the hope of much better malaria control and eventual eradication. If taken full advantage of, the strengths of the monoclonal antibody approach and the challenges it presents point us toward the possibilities of a malaria-free world. And with that possibility, we might finally see better health conditions for many of those in the 50 percent or more who are at risk of attack. Ferenc Pekár is an Associate Professor of Parasitology at Eötvös Loránd University in Hungary.
