Targeting PfProhibitin 2-Hu-Hsp70A1A complex as a unique approach towards malaria vaccine development

Autor: Manisha Marothia, Ankita Behl, Preeti Maurya, Monika Saini, Rumaisha Shoaib, Swati Garg, Geeta Kumari, Shreeja Biswas, Akshay Munjal, Sakshi Anand, Amandeep Kaur Kahlon, Pragya Gupta, Saurav Biswas, Bidhan Goswami, Haider Thaer Abdulhameed Almuqdadi, Ipsita Pal Bhowmick, Maxim Shevtsov, Sivaprakash Ramalingam, Anand Ranganathan, Shailja Singh
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: iScience, Vol 27, Iss 6, Pp 109918- (2024)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2024.109918
Popis: Summary: Malaria parasite invasion to host erythrocytes is mediated by multiple interactions between merozoite ligands and erythrocyte receptors that contribute toward the development of disease pathology. Here, we report a novel antigen Plasmodium prohibitin “PfPHB2” and identify its cognate partner “Hsp70A1A” in host erythrocyte that plays a crucial role in mediating host-parasite interaction during merozoite invasion. Using small interfering RNA (siRNA)- and glucosamine-6-phosphate riboswitch (glmS) ribozyme-mediated approach, we show that loss of Hsp70A1A in red blood cells (RBCs) or PfPHB2 in infected red blood cells (iRBCs), respectively, inhibit PfPHB2-Hsp70A1A interaction leading to invasion inhibition. Antibodies targeting PfPHB2 and monoclonal antibody therapeutics against Hsp70A1A efficiently block parasite invasion. Recombinant PfPHB2 binds to RBCs which is inhibited by anti-PfPHB2 antibody and monoclonal antibody against Hsp70A1A. The validation of PfPHB2 to serve as antigen is further supported by detection of anti-PfPHB2 antibody in patient sera. Overall, this study proposes PfPHB2 as vaccine candidate and highlights the use of monoclonal antibody therapeutics for future malaria treatment.
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