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Plasmodium falciparum multidomain protein VAR2CSA stands today as the leading vaccine candidate against pregnancy-associated malaria (PAM). Most of the studies aiming to decrypt how naturally acquired immunity develops have assessed the immune recognition of individual VAR2CSA Duffy-binding-like (DBL) domains, thus overlooking the presence of conformational epitopes resulting from the overall folding of the full-length protein. In order to characterize the development of humoral immunity toward VAR2CSA, we made use of a large cohort of 293 Senegalese pregnant women to assess the level of recognition by plasma IgG of the full-length VAR2CSA protein of the 3D7 parasite strain (3D7-VAR2CSA), the CSA-binding multidomains 3D7-DBL1X to -DBL3X (3D7-DBL1X-3X), and the CSA nonbinding multidomains 3D7-DBL4ε to -DBL6ε (3D7-DBL4ε-6ε), as well as individual 3D7-DBL domains. Our results revealed a parity-dependent recognition of the full-length 3D7-VAR2CSA and of the CSA-binding region, 3D7-DBL1X-3X. Indeed, multigravid women possess significantly higher levels of antibodies directed against these constructs than primigravidae. Our results suggest an important role of antibodies targeting the CSA-binding region in the development of immunity against PAM, therefore providing new insights on how natural protection might be acquired and further information for the design of VAR2CSA-based vaccines.

Titel:	Parity-dependent recognition of DBL1X-3X suggests an important role of the VAR2CSA high-affinity CSA-binding region in the development of the humoral response against placental malaria.
Autor/in / Beteiligte Person:	Dechavanne, S ; Srivastava, A ; Gangnard, S ; Nunes-Silva, S ; Dechavanne, C ; Fievet, N ; Deloron, P ; Chêne, A ; Gamain, B
Link:	Full Text Finder (Volltext)
Zeitschrift:	Infection and immunity, Jg. 83 (2015-06-01), Heft 6, S. 2466-74
Veröffentlichung:	Washington, DC : American Society For Microbiology ; <i>Original Publication</i>: [Bethesda, Md.] American Society for Microbiology., 2015
Medientyp:	academicJournal
ISSN:	1098-5522 (electronic)
DOI:	10.1128/IAI.03116-14
Schlagwort:	Adolescent Adult Female Humans Immunity, Humoral Infectious Disease Transmission, Vertical Middle Aged Parity Pregnancy Protein Binding Protein Structure, Tertiary Senegal epidemiology Young Adult Antigens, Protozoan metabolism DNA Repair Enzymes metabolism Gene Expression Regulation physiology Malaria, Falciparum immunology Plasmodium falciparum metabolism Transcription Factors metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Infect Immun] 2015 Jun; Vol. 83 (6), pp. 2466-74. <i>Date of Electronic Publication: </i>2015 Mar 30. MeSH Terms: Antigens, Protozoan / metabolism ; DNA Repair Enzymes / metabolism ; Gene Expression Regulation / physiology ; Malaria, Falciparum / immunology ; Plasmodium falciparum / metabolism ; Transcription Factors / metabolism ; Adolescent ; Adult ; Female ; Humans ; Immunity, Humoral ; Infectious Disease Transmission, Vertical ; Middle Aged ; Parity ; Pregnancy ; Protein Binding ; Protein Structure, Tertiary ; Senegal / epidemiology ; Young Adult References: J Biol Chem. 2012 Jul 6;287(28):23332-45. (PMID: 22570492) ; J Biol Chem. 2013 Nov 8;288(45):32106-17. (PMID: 24043627) ; Science. 1996 Jun 7;272(5267):1502-4. (PMID: 8633247) ; Malar Res Treat. 2011;2011:764845. (PMID: 22363896) ; Infect Immun. 2005 May;73(5):2841-7. (PMID: 15845489) ; Infect Immun. 2014 Jun;82(6):2565-73. (PMID: 24686068) ; Infect Immun. 2003 Nov;71(11):6620-3. (PMID: 14573685) ; J Infect Dis. 2012 Dec 15;206(12):1911-9. (PMID: 23045626) ; J Infect Dis. 2006 Mar 1;193(5):713-20. (PMID: 16453268) ; Infect Immun. 2012 Apr;80(4):1479-90. (PMID: 22331427) ; Placenta. 2004 May;25(5):359-78. (PMID: 15081631) ; J Biol Chem. 2008 Aug 8;283(32):21842-6. (PMID: 18550531) ; Infect Immun. 2002 Dec;70(12):6948-60. (PMID: 12438374) ; Protein Expr Purif. 2014 Mar;95:188-94. (PMID: 24380803) ; Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):4884-9. (PMID: 20194779) ; PLoS One. 2010;5(2):e9230. (PMID: 20169064) ; Malar J. 2009;8:19. (PMID: 19166589) ; Methods Mol Biol. 2013;923:307-19. (PMID: 22990788) ; Mol Biochem Parasitol. 2007 Oct;155(2):103-12. (PMID: 17669514) ; Microbes Infect. 2006 Nov-Dec;8(14-15):2863-71. (PMID: 17095277) ; J Biol Chem. 2011 May 6;286(18):15908-17. (PMID: 21398524) ; J Infect Dis. 2007 Jul 1;196(1):155-64. (PMID: 17538896) ; Malar J. 2008;7:10. (PMID: 18190692) ; J Infect Dis. 2001 Sep 1;184(5):618-26. (PMID: 11494167) ; Nat Struct Mol Biol. 2008 Sep;15(9):932-8. (PMID: 19172746) ; J Mol Biol. 2009 Oct 16;393(1):202-13. (PMID: 19695262) ; PLoS One. 2014;9(2):e88173. (PMID: 24505415) ; J Exp Med. 2004 Nov 1;200(9):1197-203. (PMID: 15520249) ; Nat Struct Mol Biol. 2011 Aug;18(8):908-14. (PMID: 21743458) ; Trop Med Int Health. 1998 Aug;3(8):667-77. (PMID: 9735937) ; PLoS Pathog. 2014 Jan;10(1):e1003869. (PMID: 24415938) ; Lancet Infect Dis. 2007 Feb;7(2):93-104. (PMID: 17251080) ; Parasitology. 2007;134(Pt 13):1871-6. (PMID: 17958922) ; J Infect Dis. 2005 Mar 15;191(6):1010-3. (PMID: 15717280) ; Lancet. 2004 Jan 24;363(9405):283-9. (PMID: 14751701) ; J Immunol. 2000 Sep 15;165(6):3309-16. (PMID: 10975848) ; J Mol Biol. 2010 Apr 2;397(3):826-34. (PMID: 20109466) ; Parasite Immunol. 1995 Jan;17(1):1-10. (PMID: 7731730) ; Infect Immun. 2006 Oct;74(10):5955-63. (PMID: 16988275) ; Nature. 1998 Oct 29;395(6705):851-2. (PMID: 9804416) ; PLoS One. 2012;7(1):e31011. (PMID: 22295123) ; PLoS One. 2012;7(6):e40049. (PMID: 22761948) ; Mol Microbiol. 2003 Jul;49(1):179-91. (PMID: 12823820) ; PLoS One. 2011;6(5):e20270. (PMID: 21625526) Substance Nomenclature: 0 (Antigens, Protozoan) ; 0 (ERCC8 protein, human) ; 0 (Transcription Factors) ; 0 (VAR2CSA protein, Plasmodium falciparum) ; EC 6.5.1.- (DNA Repair Enzymes) Entry Date(s): Date Created: 20150401 Date Completed: 20150728 Latest Revision: 20181113 Update Code: 20231215 PubMed Central ID: PMC4432739

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Parity-dependent recognition of DBL1X-3X suggests an important role of the VAR2CSA high-affinity CSA-binding region in the development of the humoral response against placental malaria.