Targeting PfProhibitin 2-Hu-Hsp70A1A complex as a unique approach towards malaria vaccine development
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
Affiliations
Manisha Marothia
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India
Ankita Behl
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India
Preeti Maurya
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India
Monika Saini
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India
Rumaisha Shoaib
Department of Bioscience, Jamia Millia Islamia, New Delhi, India
Swati Garg
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India
Geeta Kumari
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India
Shreeja Biswas
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India
Akshay Munjal
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India
Sakshi Anand
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India
Amandeep Kaur Kahlon
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India
Pragya Gupta
CSIR-Institute of Genomics and Integrative Biology, Mathura Road, Sukhdev Vihar, New Delhi 110025, India
Saurav Biswas
Regional Medical Research Center-Northeast Region (RMRC-NE)-ICMR, Dibrugarh 786001, India
Bidhan Goswami
Multidisciplinary Research Unit, Agartala Government Medical College, Agartala, Tripura (West), India
Haider Thaer Abdulhameed Almuqdadi
Department of Bioscience, Jamia Millia Islamia, New Delhi, India; Department of Chemistry, College of Science, Al-Nahrain University, Baghdad, Iraq
Ipsita Pal Bhowmick
Regional Medical Research Center-Northeast Region (RMRC-NE)-ICMR, Dibrugarh 786001, India
Maxim Shevtsov
Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany; Institute of Cytology of the Russian Academy of Sciences (RAS), 194064 St. Petersburg, Russia; Personalized Medicine Centre, Almazov National Medical Research Centre, Akkuratova Str. 2, 197341 St. Petersburg, Russia
Sivaprakash Ramalingam
CSIR-Institute of Genomics and Integrative Biology, Mathura Road, Sukhdev Vihar, New Delhi 110025, India
Anand Ranganathan
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India; Corresponding author
Shailja Singh
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India; Corresponding author
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.
