Proteolytic Cleavage of the Plasmodium falciparum Circumsporozoite Protein Is a Target of Protective Antibodies

The Journal of Infectious Diseases
Diego A EspinosaF Zavala

Abstract

Studies in animals and human volunteers demonstrate that antibodies against the repeat-region of the Plasmodium circumsporozoite protein (CSP) abrogate sporozoite infection. However, the realization that the N- and C- terminal regions flanking the repeats play essential roles in parasite infectivity raised the possibility that they could be targeted by protective antibodies. We characterized a monoclonal antibody (mAb5D5) specific for the N-terminus of the P. falciparum CSP, which inhibits the proteolytic cleavage of the CSP, a key requirement for parasite infection of hepatocytes. Adoptive transfer of mAb5D5 strongly inhibits the in vivo infection of sporozoites expressing the N-terminus of P. falciparum CSP, and this protection is greatly enhanced when combined with antirepeat antibodies. Our results show that antibodies interfering with molecular processes required for parasite infectivity can exert a strong in vivo protective activity and indicate that pre-erythrocytic vaccines against Plasmodium should include the CSP N-terminal region.

References

Nov 1, 1987·The Journal of Experimental Medicine·F ZavalaV Nussenzweig
Feb 12, 1998·Methods : a Companion to Methods in Enzymology·R Ménard, C Janse
Dec 10, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Cathrine PerssonElizabeth Nardin
Jan 5, 2005·The Journal of Experimental Medicine·Alida CoppiPhotini Sinnis
Oct 20, 2011·The New England Journal of Medicine·UNKNOWN RTS,S Clinical Trials PartnershipPreeti Vansadia
Nov 10, 2012·The New England Journal of Medicine·UNKNOWN RTS,S Clinical Trials PartnershipPreeti Vansadia

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Citations

Jul 15, 2016·Reproductive Toxicology·Lusine YaghjyanSu-Hsin Chang
Mar 10, 2017·Expert Review of Vaccines·Brandon SackD Noah Sather
Jul 20, 2017·The Korean Journal of Parasitology·Seon-Hee KimHyun-Jong Yang
Jan 10, 2019·PloS One·Erwan AtchesonArturo Reyes-Sandoval
Aug 14, 2020·The Journal of Experimental Medicine·Elaine ThaiElena A Levashina
Aug 30, 2019·Nature Reviews. Immunology·Jean-Philippe Julien, Hedda Wardemann
Jun 25, 2019·Frontiers in Immunology·Yun Shan GohLaurent Rénia
Jan 29, 2020·Proceedings of the National Academy of Sciences of the United States of America·Mark D LangowskiSheetij Dutta
Apr 9, 2017·Cold Spring Harbor Perspectives in Medicine·Carole A Long, Fidel Zavala
Jan 9, 2019·Frontiers in Immunology·Eduardo L V SilveiraIrene S Soares
Oct 24, 2018·Nature Microbiology·Eduardo AliprandiniRogerio Amino
Apr 6, 2019·Frontiers in Immunology·Janna HeideJulian Schulze Zur Wiesch
Sep 22, 2017·Human Vaccines & Immunotherapeutics·Philippe MorisRobbert G van der Most
May 12, 2017·Cold Spring Harbor Perspectives in Medicine·Julie HealerAshley J Birkett
May 1, 2018·Peptide Science·Christopher A MacRaildRaymond S Norton
Jan 22, 2017·Cold Spring Harbor Perspectives in Medicine·Friedrich Frischknecht, Kai Matuschewski
Nov 27, 2020·Microbiology and Molecular Biology Reviews : MMBR·Gunnar Lindahl
Feb 9, 2021·Expert Review of Vaccines·Deepyan Chatterjee, Ian Andrew Cockburn
Jun 25, 2021·Science Translational Medicine·Joshua TanPeter D Crompton

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