학술논문
Targeting PfProhibitin 2-Hu-Hsp70A1A complex as a unique approach towards malaria vaccine development
Document Type
article
Author
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
Source
iScience, Vol 27, Iss 6, Pp 109918- (2024)
Subject
Language
English
ISSN
2589-0042
Abstract
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.