دورية أكاديمية
A novel CSP C-terminal epitope targeted by an antibody with protective activity against Plasmodium falciparum.
| العنوان: | A novel CSP C-terminal epitope targeted by an antibody with protective activity against Plasmodium falciparum. |
|---|---|
| المؤلفون: | Beutler N; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, United States of America., Pholcharee T; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America., Oyen D; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America., Flores-Garcia Y; Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America., MacGill RS; PATH's Malaria Vaccine Initiative, Washington, District of Columbia, United States of America., Garcia E; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, United States of America., Calla J; Department of Pediatrics, University of California, San Diego, School of Medicine, La Jolla, California, United States of America., Parren M; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, United States of America., Yang L; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, United States of America., Volkmuth W; Atreca Inc., South San Francisco, California, United States of America., Locke E; PATH's Malaria Vaccine Initiative, Washington, District of Columbia, United States of America., Regules JA; Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America., Dutta S; Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America., Emerling D; Atreca Inc., South San Francisco, California, United States of America., Early AM; Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America., Neafsey DE; Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America., Winzeler EA; Department of Pediatrics, University of California, San Diego, School of Medicine, La Jolla, California, United States of America., King CR; PATH's Malaria Vaccine Initiative, Washington, District of Columbia, United States of America., Zavala F; Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America., Burton DR; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, United States of America.; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, Massachusetts, United States of America., Wilson IA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America.; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, United States of America., Rogers TF; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, United States of America.; Division of Infectious Diseases, Department of Medicine, University of California, San Diego, La Jolla, California, United States of America. |
| المصدر: | PLoS pathogens [PLoS Pathog] 2022 Mar 28; Vol. 18 (3), pp. e1010409. Date of Electronic Publication: 2022 Mar 28 (Print Publication: 2022). |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: San Francisco, CA : Public Library of Science, c2005- |
| مواضيع طبية MeSH: | Malaria* , Malaria Vaccines* , Malaria, Falciparum*/prevention & control, Animals ; Antibodies, Protozoan ; Epitopes ; Humans ; Mice ; Plasmodium falciparum ; Protozoan Proteins/genetics |
| مستخلص: | Potent and durable vaccine responses will be required for control of malaria caused by Plasmodium falciparum (Pf). RTS,S/AS01 is the first, and to date, the only vaccine that has demonstrated significant reduction of clinical and severe malaria in endemic cohorts in Phase 3 trials. Although the vaccine is protective, efficacy declines over time with kinetics paralleling the decline in antibody responses to the Pf circumsporozoite protein (PfCSP). Although most attention has focused on antibodies to repeat motifs on PfCSP, antibodies to other regions may play a role in protection. Here, we expressed and characterized seven monoclonal antibodies to the C-terminal domain of CSP (ctCSP) from volunteers immunized with RTS,S/AS01. Competition and crystal structure studies indicated that the antibodies target two different sites on opposite faces of ctCSP. One site contains a polymorphic region (denoted α-ctCSP) and has been previously characterized, whereas the second is a previously undescribed site on the conserved β-sheet face of the ctCSP (denoted β-ctCSP). Antibodies to the β-ctCSP site exhibited broad reactivity with a diverse panel of ctCSP peptides whose sequences were derived from field isolates of P. falciparum whereas antibodies to the α-ctCSP site showed very limited cross reactivity. Importantly, an antibody to the β-site demonstrated inhibition activity against malaria infection in a murine model. This study identifies a previously unidentified conserved epitope on CSP that could be targeted by prophylactic antibodies and exploited in structure-based vaccine design. Competing Interests: We have read the journal’s policy and the authors of this manuscript have the following competing interests. The authors N.B., T.P., D.O., Y.F.G., R.S.M., E.G., J.C., M.P., L.Y., E.L., J.A.R., S.D., A.M.E., D.E.N., E.W., C.R.K., F.Z., D.R.B., I.A.W., and T.F.R. declare that they have no competing interests. W.V., D.E. were or are employees of Atreca, Inc. and own equity in Atreca, Inc. |
| References: | Lancet Infect Dis. 2015 Dec;15(12):1450-8. (PMID: 26342424) Malar J. 2019 Dec 18;18(1):426. (PMID: 31849326) Acta Crystallogr D Biol Crystallogr. 2010 Jan;66(Pt 1):12-21. (PMID: 20057044) Lancet Infect Dis. 2017 May;17(5):498-509. (PMID: 28216244) Hum Vaccin Immunother. 2020 Mar 3;16(3):480-489. (PMID: 31545128) Science. 2018 Jun 22;360(6395):1358-1362. (PMID: 29880723) Nat Commun. 2021 Feb 16;12(1):1063. (PMID: 33594061) Clin Vaccine Immunol. 2012 Mar;19(3):377-85. (PMID: 22237895) Science. 1985 Jun 21;228(4706):1436-40. (PMID: 2409595) J Infect Dis. 2016 Sep 1;214(5):762-71. (PMID: 27296848) Malar J. 2009 Jun 05;8:120. (PMID: 19500348) PLoS Pathog. 2020 Mar 9;16(3):e1008373. (PMID: 32150583) J Exp Med. 2018 Jan 2;215(1):63-75. (PMID: 29167197) J Mol Biol. 2020 Feb 14;432(4):1048-1063. (PMID: 31883801) Sci Adv. 2018 Oct 10;4(10):eaau8529. (PMID: 30324137) Nat Commun. 2019 May 15;10(1):2174. (PMID: 31092823) J Exp Med. 1994 Jul 1;180(1):297-306. (PMID: 8006589) Lancet. 2021 May 15;397(10287):1809-1818. (PMID: 33964223) N Engl J Med. 2015 Nov 19;373(21):2025-2037. (PMID: 26488565) Vaccine. 2021 Feb 5;39(6):968-975. (PMID: 33431225) Malar J. 2020 Mar 17;19(1):113. (PMID: 32183833) Proc Natl Acad Sci U S A. 2017 Nov 28;114(48):E10438-E10445. (PMID: 29138320) Nat Med. 2018 May;24(4):401-407. (PMID: 29554084) Methods Enzymol. 1997;276:307-26. (PMID: 27754618) N Engl J Med. 2021 Aug 26;385(9):803-814. (PMID: 34379916) J Exp Med. 1993 May 1;177(5):1287-98. (PMID: 8478608) Mol Microbiol. 2002 Aug;45(3):637-51. (PMID: 12139612) J Mol Biol. 1994 May 20;238(5):777-93. (PMID: 8182748) Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11889-94. (PMID: 8876233) J Infect Dis. 2015 Oct 1;212(7):1111-9. (PMID: 25762791) Immunity. 2017 Dec 19;47(6):1197-1209.e10. (PMID: 29195810) N Engl J Med. 2011 Nov 17;365(20):1863-75. (PMID: 22007715) Cell Rep. 2021 Apr 13;35(2):108996. (PMID: 33852850) Sci Transl Med. 2020 Jul 22;12(553):. (PMID: 32718991) PLoS One. 2012;7(8):e43430. (PMID: 22912873) Nat Med. 2020 Jul;26(7):1135-1145. (PMID: 32451496) Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501. (PMID: 20383002) J Biol Chem. 2002 Dec 6;277(49):47613-8. (PMID: 12244064) Lancet. 2013 Nov 23;382(9906):1700-1. (PMID: 24239252) Front Immunol. 2014 Jun 02;5:250. (PMID: 24917864) PLoS Med. 2014 Jul 29;11(7):e1001685. (PMID: 25072396) Cell Host Microbe. 2007 Nov 15;2(5):316-27. (PMID: 18005753) Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21. (PMID: 20124702) Immunity. 2020 Oct 13;53(4):733-744.e8. (PMID: 32946741) Proc Natl Acad Sci U S A. 2012 May 15;109(20):7817-22. (PMID: 22547819) Science. 1984 Aug 10;225(4662):593-9. (PMID: 6204383) Clin Immunol. 2014 Mar;151(1):55-65. (PMID: 24525048) J Mol Graph. 1993 Jun;11(2):139-41. (PMID: 8347567) Vaccine. 2010 Jul 12;28(31):4880-94. (PMID: 20553771) N Engl J Med. 2016 Jun 30;374(26):2519-29. (PMID: 27355532) Malar J. 2014 Nov 23;13:452. (PMID: 25418416) J Biol Chem. 2009 Sep 25;284(39):26951-63. (PMID: 19633296) Nat Med. 2018 May;24(4):408-416. (PMID: 29554083) J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674. (PMID: 19461840) Cell Host Microbe. 2020 Oct 7;28(4):572-585.e7. (PMID: 32697938) |
| معلومات مُعتمدة: | INV-004923 United States GATES Bill & Melinda Gates Foundation; P41 GM103393 United States GM NIGMS NIH HHS |
| المشرفين على المادة: | 0 (Antibodies, Protozoan) 0 (Epitopes) 0 (Malaria Vaccines) 0 (Protozoan Proteins) |
| تواريخ الأحداث: | Date Created: 20220328 Date Completed: 20220411 Latest Revision: 20240513 |
| رمز التحديث: | 20240513 |
| مُعرف محوري في PubMed: | PMC8989322 |
| DOI: | 10.1371/journal.ppat.1010409 |
| PMID: | 35344575 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder كن أول من يترك تعليقا!