Monoclonal Antibody Treatments for Malaria

Human infection with a parasite called Plasmodium falciprum causes life-threatening malaria. This occurs after mosquitoes transmit these parasites through their bites. According to the World Health Organization (WHO), the estimated malaria cases in 2023 reached 263 million globally, together with 597,000 fatalities, while the WHO African Region suffered the most from the disease. Almost all malaria deaths among the population segment below five years occurred in the African Region [1].

Did you know? In 2023, the African region held responsibility for 94 percent of worldwide malaria cases, totaling 246 million. It was found that 95% of the mortality was from malaria, amounting to 569 thousand persons.

Antimalarial drugs combined with long-lived insecticide-treated nets (LLIMs), insect larvae control, and indoor insecticide residue spraying (IRS) have substantially decreased malaria disease influence. Drug resistance, together with logistical challenges for vaccine dissemination, continues to be a major obstacle [2].

Advancements now offer monoclonal antibodies (mAbs) as new and effective approaches for preventing and treating malaria infections. Current research demonstrates that mAbs provide complete malaria prevention during controlled human infections, along with 88% effectiveness for six months in environments where malaria is endemic. Researchers have not published enough information about the manufacturing requirements of this product [3].

Understanding Monoclonal Antibodies

A labelled diagram showing the production of monoclonal antibodies. Source: https://upload.wikimedia.org/wikipedia/commons/9/9a/Monoclonals.png

Monoclonal antibodies (mAbs) are lab-engineered molecules that replicate the immune system's ability to combat harmful pathogens and diseased cells. These medicinally designed antibodies focus on targeting one antigen with great accuracy.

The precise antigen-targeting capacity of these molecules makes them a strong treatment option for multiple medical conditions. These have introduced themselves as crucial therapeutic tools that now dominate modern medical practice. The production of monoclonal antibodies depends on two main technological approaches, which include hybridoma (fusion of myeloma and plasma cells) and recombinant DNA techniques.

Traditional drugs target pathogens in broad ways, but mAbs use engineering to connect with precise surface proteins of pathogens, thereby allowing accurate neutralization. This specificity reduces the risk of side effects and increases treatment efficacy [4].

Malaria: Challenges in Treatment and Prevention

The fight against malaria faces several obstacles:

Drug Resistance: The growing resistance of Plasmodium falciparum to antimalarial drugs threatens global malaria control efforts. Chloroquine and sulfadoxine-pyrimethamine (SP) are becoming less effective. This leads to rising cases, deaths, and economic and social burdens [5].
Vaccine Limitations: The approval of RTS,S, and R21 malaria vaccines presents a new opportunity in malaria eradication. However, their moderate efficacy and large-scale distribution challenges remain concerns [6].
Accessibility: Remote regions often lack the infrastructure for effective distribution of treatments and preventive measures [7].

These challenges demand the need for innovative approaches like monoclonal antibody therapies.

Monoclonal Antibody-Based Treatments for Malaria

Monoclonal antibodies offer a novel strategy by targeting specific stages of the malaria parasite's life cycle. These antibodies have shown promise in clinical trials, offering potential alternatives to traditional malaria prevention methods. Notable mAbs under investigation include:

CIS43LS: This antibody binds to the circumsporozoite protein (CSP) on the surface of malaria sporozoites, preventing them from infecting liver cells. In a phase 1 clinical trial, CIS43LS demonstrated high protection against parasitemia at doses of 20 mg/kg or 40 mg/kg administered intravenously [8].
L9LS: A next-generation mAb that also targets CSP. In a phase 1 trial, L9LS exhibited 88% protective efficacy against malaria infection when administered to healthy adults [9].

This table provides an overview of some of the monoclonal antibodies currently being studied for malarial disease [8,9,10].

Monoclonal Antibody	Target Antigen	Administration Route	Efficacy	Clinical Trial Phase
CIS43LS	Circumsporozoite Protein (CSP)	Intravenous (IV)	Up to 88.2% effective over a 24-week period in Malian adults	Phase 2
L9LS	Circumsporozoite Protein (CSP)	Subcutaneous (SC)	77% effective over a 6-month period in Malian children	Phase 2
MAM01	Not specified	Not specified	Under investigation in challenge trials	Early-stage trials [10]

Advantages of Monoclonal Antibodies in Malaria Treatment

Monoclonal antibodies present several benefits:

Long-Lasting Protection: A single administration can protect for several months, covering entire malaria transmission seasons in endemic areas [11].
High Specificity: mAbs precisely target malaria parasites, reducing collateral damage to the body's cells and minimizing side effects.
Potential in Eradication Efforts: By effectively preventing infection, mAbs could play a crucial role in reducing transmission rates and moving towards malaria eradication.

Challenges and Limitations

Despite their promise, mAb treatments face challenges:

Production Costs: Manufacturing mAbs is expensive, potentially limiting access in low-income regions where malaria is most prevalent.
Storage Requirements: Many mAbs require refrigeration, posing logistical challenges in areas with limited infrastructure.
Accessibility: Ensuring equitable distribution to remote and underserved communities remains a significant hurdle.
Potential Resistance: There's a risk that malaria parasites could develop resistance to mAbs, necessitating ongoing monitoring and adaptation of therapies.

Conclusion

Medical science has identified monoclonal antibody treatments as a promising new method for combating malaria due to their targeted durability. Ongoing research promises solutions to address current challenges about affordability and accessibility and possible resistance issues through ongoing innovation.

The future development of these treatment methods will lower the worldwide impact of malaria and bring medical authorities one step closer to believing that eradication is achievable.

References:

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Moehrle JJ. Development of New Strategies for Malaria Chemoprophylaxis: From Monoclonal Antibodies to Long-Acting Injectable Drugs. Trop Med Infect Dis [Internet]. 2022 [cited 2025 Mar 27]; 7(4):58. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9024890/.
Lyke KE, Berry AA, Mason K, Idris AH, O’Callahan M, Happe M, et al. Low-dose intravenous and subcutaneous CIS43LS monoclonal antibody for protection against malaria (VRC 612 Part C): a phase 1, adaptive trial. Lancet Infect Dis. 2023; 23(5):578–88.
Nekkab N, Penny MA. Accelerated development of malaria monoclonal antibodies. Cell Rep Med [Internet]. 2022 [cited 2025 Mar 27]; 3(10):100786. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9589116/.
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Challenger JD, Beek SW van, Heine R ter, Boor SC van der, Charles GD, Smit MJ, et al. Modeling the Impact of a Highly Potent Plasmodium falciparum Transmission-Blocking Monoclonal Antibody in Areas of Seasonal Malaria Transmission. J Infect Dis [Internet]. 2023 [cited 2025 Mar 27]; 228(2):212–23. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10345482/.

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