Targeting Pf Prohibitin 2-Hu-Hsp70A1A complex as a unique approach towards malaria vaccine development.

Autor:	Marothia M; Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India., Behl A; Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India., Maurya P; Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India., Saini M; Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India., Shoaib R; Department of Bioscience, Jamia Millia Islamia, New Delhi, India., Garg S; Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India., Kumari G; Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India., Biswas S; Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India., Munjal A; Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India., Anand S; Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India., Kahlon AK; Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India., Gupta P; CSIR-Institute of Genomics and Integrative Biology, Mathura Road, Sukhdev Vihar, New Delhi 110025, India., Biswas S; Regional Medical Research Center-Northeast Region (RMRC-NE)-ICMR, Dibrugarh 786001, India., Goswami B; Multidisciplinary Research Unit, Agartala Government Medical College, Agartala, Tripura (West), India., Abdulhameed Almuqdadi HT; Department of Bioscience, Jamia Millia Islamia, New Delhi, India.; Department of Chemistry, College of Science, Al-Nahrain University, Baghdad, Iraq., Bhowmick IP; Regional Medical Research Center-Northeast Region (RMRC-NE)-ICMR, Dibrugarh 786001, India., Shevtsov M; 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., Ramalingam S; CSIR-Institute of Genomics and Integrative Biology, Mathura Road, Sukhdev Vihar, New Delhi 110025, India., Ranganathan A; Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India., Singh S; Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2024 May 07; Vol. 27 (6), pp. 109918. Date of Electronic Publication: 2024 May 07 (Print Publication: 2024).
DOI:	10.1016/j.isci.2024.109918
Abstrakt:	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 " Pf PHB2" 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 Pf PHB2 in infected red blood cells (iRBCs), respectively, inhibit Pf PHB2-Hsp70A1A interaction leading to invasion inhibition. Antibodies targeting Pf PHB2 and monoclonal antibody therapeutics against Hsp70A1A efficiently block parasite invasion. Recombinant Pf PHB2 binds to RBCs which is inhibited by anti- Pf PHB2 antibody and monoclonal antibody against Hsp70A1A. The validation of Pf PHB2 to serve as antigen is further supported by detection of anti- Pf PHB2 antibody in patient sera. Overall, this study proposes Pf PHB2 as vaccine candidate and highlights the use of monoclonal antibody therapeutics for future malaria treatment. Competing Interests: The authors declare no competing interests. (© 2024 The Authors. Published by Elsevier Inc.)
Databáze:	MEDLINE
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