Exosome-based malaria vaccine, a miracle of nanomedicine

Abstract

Exosomes are the nano-size subpopulation of extracellular vesicles secreted by all living cells and they originated from the endosomes. In general, it is involved in Inter-Cellular communication. Exosomes transport several bioactive molecules (DNA, RNA, protein, etc.) from parental cells to recipient cells. This event showcases cellular health or pathologic status1. The invention of the exosome adds a new chapter in nanomedicine. After the event now nanomedicine overcome several limitations (toxicity, immune rejection, biocompatibility, stability, and target-specific drug transport). The current decade of scientific investigation suggests that exosomes have active participation in host-pathogen intercellular communication in several parasitic infected diseases including malaria2. Malaria is a lethal parasitic infectious disease that led to large population death globally. It is spared in the human host after biting of parasite load female anopheles bite. This parasitic development happens in a circulating system with red bold cells and this maturation face boosts of exosome secretion3. In Malaria ABCA1 (ATP-binding-cassette transporter 1) gene is most vital for exosome biogenesis and maintaining host-pathogen communication4. Experimental data shows that the ABCA1 gene knockout reduces the chance of cerebral Malaria5. In disease progression phage host-pathogen cell-to-cell interaction happens via exosome cargos miRNA and proteins, Both ingredients of exosome efficiently regulate genetic expression. Malaria-infected cells derived exosomes carry miRNA451a which is related to red blood cells (RBC) maturation and related to vascular permeability. Malaria derives exosome-associated noncoding RNA, and fragments of genomic DNA of Plasmodium involved in suppressing the innate immune cells activity6. The immune system suppresses during malaria, and infected RBCs derive exosome (Fig. 1) downregulation natural killer cell activity against parasites. Infected RBCs-derived exosome protein and inflammatory molecules suppress the immune system. During malaria, exosomes play a vital role in reducing T-cell proliferation and downregulating T-cell–mediated immune response7. The vaccine development for Malaria is most challenging because of the complex life cycle of Plasmodium and surface protein diversity, although some limited success stories there8. At the current time, large-scale malaria vaccine development and delivery focus on exosomes9. Exosome-based plasmid delivery plays the role in anti-malaria antigenic immune memory development and promotes humoral immunity10. In malarial, exosome is the most promising drug resistance overcoming tool. Although exosome-based vaccine needs more clinical investigation, it is the most efficient, has less immunogenic rejection, and it is capable across biological braise. The infected RBC derives exosome-related miRNA is the most exciting part of the malaria Vaccine research but it required deep investigation before being used. Infected RBC derives exosome-related mediated host immune system reprogramming is still unexplored side of the exosome-based malaria research domain. Detailed investigation is needed regarding host cells derived exosome cargos (inflammatory molecules, miRNAs) and malaria development multiple stages associate exosome heterogeneity11 to develop exosome base efficient malaria vaccine. Now the question comes about why malaria research focuses on exosomes? The exosome-based malarial treatment approach is innovative because it supports early diagnosis and therapeutic aspects it is more promising with null toxicity with less immune rejection, compare with the other approaches, exosomes have some advantages such as boosting the immune system against malaria, surface engineering exosomes are more efficient compared with other (liposome) approaches in drug delivery in the case of malaria. Exosome is a smart tool for malarial drug delivery because they provide better stability of the drug in the biological system and help them cross the biological barriers. The feasible aspect of exosome-based malaria research depends on the expertise in exosome research. It is possible if we develop an expert group and some of the exosome-related advanced equipment. Once this facility is established and maintained by a trained expert, that reduces the production cost of the downstream product. Exosome-based malarial treatment research adds a new chapter to parasitology research. Exosome helps to decode the malaria-associated pathological complication at the more detailed molecular level. We hope, this innovative approach will save large-scale populations from malaria globally.Figure 1: Exosome and malaria. (A) Infected red blood cells (RBCs) derive exosomes that inhibit RBCs development and suppression of immune response against malaria. (B) Exosome surface modification, drug delivery an innovative approach in exosome associate malaria vaccine development.Ethical approval and consent of publication None. Sources of funding None. Author contribution D.M. and R.D. has conceptualized the project. D.M., S.G., R.M., P.S.G., and A.A. have written the manuscript. A.D. and S.K.J. has guided the project. All authors have done the editing. All authors have contributed significantly in preparation of the manuscript. Conflict of interest disclosure The authors declare that they have no financial conflict of interest with regard to the content of this report. Research registration unique identifying number (UIN) Not Applicable. Guarantor All Authors. Availability of data and materials None.