IgA, or immunoglobulin A antibody is well documented for its crucial role in defending against mucosally acquired pathogens. However, its specific function in immune responses to non-mucosal pathogens such as Plasmodium falciparum, the causative agent of the deadly malaria, remains unclear despite IgA being the second-most abundant antibody class in the bloodstream. A research study titled "Functional human IgA targets a conserved site on malaria sporozoites" published in the acclaimed international journal Science Translational Medicine has offered new insights into the relationship between malaria and the human IgA antibody. The researchers suggest that IgA could potentially target and neutralize malaria sporozoites, an idea previously unexplored by the scientific community.
Understanding the Role of IgA Antibodies in Malaria Defense:
In a groundbreaking move, the team of researchers from institutions such as the US National Institute of Allergy and Infectious Diseases focused their studies on a population in Mali, West Africa, revealing that the presence of active IgA antibodies in individuals leads to effective resistance against malaria infection. Malaria, caused by five types of Plasmodium species, impairs red blood cells, inducing joint pain, fever, hemolytic anemia, and increased blood protein levels. This disease is spread when a female Anopheles mosquito transfers sporozoites into the host's bloodstream during a bite. The focus of the new research is on malaria caused by Plasmodium falciparum because of its strong correlation with higher disease morbidity and death rates in populations. Remarkably, when the Malian IgA antibodies were introduced to laboratory mice infected with malaria, the parasite load in the mice decreased significantly. The researchers were able to isolate a particular monoclonal IgA antibody known as MAD2-6, from individuals who showed resistance to malaria. This antibody latches onto a highly conserved epitope found at the CSP protein's amino terminus, a major surface protein of the sporozoite.
Fig 1. Naturally acquired IgA mAbs reduce sporozoite infection in vivo.1
Implications for Future Malaria Treatment Strategies
This research not only targeted local inhabitants of Mali but also encompassed a broader spectrum of populations, including those naturally immune to the disease due to exposure to infected mosquitoes. Interestingly, it was discovered that the body could be induced to produce circulating IgA in the presence of the sporozoites, the mobile sporocyst stage in the malaria parasite life cycle. The biological preference of IgA to target malaria parasites reflects complex behavior. Its ability to protect against pathogens, such as malaria, that mainly survive in human blood, was previously uncertain. With an alarming 200-400 million people affected by malaria annually, especially in tropical regions of the southern hemisphere and among children under five as per World Health Organization data, the identification of a new defense mechanism is significant.
In closing, the research puts forth the critical role of circulating IgA in defending against malaria. It also identifies two amino terminuses of circumsporozoite protein as potential targets for functional antibodies. These findings present a novel strategy for developing monoclonal antibody treatments for malaria, shedding new light on future malaria research, and supporting the investigation of circumsporozoite protein as a potential target for therapeutic monoclonal antibodies.
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Reference
- Tan, Joshua, et al. "Functional human IgA targets a conserved site on malaria sporozoites." Science translational medicine 13.599 (2021): eabg2344.
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