Protective antibodies target cryptic epitope unmasked by cleavage of malaria sporozoite protein.

Autor: Dacon C; Antibody Biology Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., Moskovitz R; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA., Swearingen K; Institute for Systems Biology, Seattle, WA, USA., Da Silva Pereira L; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Flores-Garcia Y; Department of Molecular Microbiology and Immunology and Johns Hopkins Malaria Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA., Aleshnick M; Vaccine and Gene Therapy Institute, Oregon Health & Science University, Portland, OR, USA., Kanatani S; Department of Molecular Microbiology and Immunology and Johns Hopkins Malaria Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA., Flynn B; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Molina-Cruz A; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., Wollenberg K; Bioinformatics & Computational Biosciences Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Traver M; Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., Kirtley P; Vaccine and Gene Therapy Institute, Oregon Health & Science University, Portland, OR, USA., Purser L; Antibody Biology Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., Dillon M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Bonilla B; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Franco A; Antibody Biology Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., Petros S; Antibody Biology Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., Kritzberg J; Antibody Biology Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., Tucker C; Antibody Biology Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.; Department of Biology, The Catholic University of America, Washington, DC, USA., Paez GG; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA., Gupta P; Seattle Children's Research Institute, Seattle, WA, USA., Shears MJ; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA., Pazzi J; Antigen Discovery, Incorporated, Irvine, CA, USA., Edgar JM; Antigen Discovery, Incorporated, Irvine, CA, USA., Teng AA; Antigen Discovery, Incorporated, Irvine, CA, USA., Belmonte A; General Dynamics Information Technology, Inc., Falls Church, VA, USA.; Agile Vaccines and Therapeutics Department, Naval Medical Research Command, Silver Spring, MD, USA., Oda K; Agile Vaccines and Therapeutics Department, Naval Medical Research Command, Silver Spring, MD, USA.; Henry M Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA., Doumbo S; Mali International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Bamako, Mali., Krymskaya L; Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., Skinner J; Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., Li S; Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., Ghosal S; Bioinformatics & Computational Biosciences Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Kayentao K; Mali International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Bamako, Mali., Ongoiba A; Mali International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Bamako, Mali., Vaughan A; Seattle Children's Research Institute, Seattle, WA, USA., Campo JJ; Antigen Discovery, Incorporated, Irvine, CA, USA., Traore B; Mali International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Bamako, Mali., Barillas-Mury C; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., Wijayalath W; Agile Vaccines and Therapeutics Department, Naval Medical Research Command, Silver Spring, MD, USA.; Henry M Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA., Idris A; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA., Crompton PD; Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., Sinnis P; Department of Molecular Microbiology and Immunology and Johns Hopkins Malaria Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA., Wilder BK; Vaccine and Gene Therapy Institute, Oregon Health & Science University, Portland, OR, USA., Zavala F; Department of Molecular Microbiology and Immunology and Johns Hopkins Malaria Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA., Seder RA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Wilson IA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, USA., Tan J; Antibody Biology Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2025 Jan 03; Vol. 387 (6729), pp. eadr0510. Date of Electronic Publication: 2025 Jan 03.
DOI: 10.1126/science.adr0510
Abstrakt: The most advanced monoclonal antibodies (mAbs) and vaccines against malaria target the central repeat region or closely related sequences within the Plasmodium falciparum circumsporozoite protein (PfCSP). Here, using an antigen-agnostic strategy to investigate human antibody responses to whole sporozoites, we identified a class of mAbs that target a cryptic PfCSP epitope that is only exposed after cleavage and subsequent pyroglutamylation (pGlu) of the newly formed N terminus. This pGlu-CSP epitope is not targeted by current anti-PfCSP mAbs and is not included in the licensed malaria vaccines. MAD21-101, the most potent mAb in this class, confers sterile protection against Pf infection in a human liver-chimeric mouse model. These findings reveal a site of vulnerability on the sporozoite surface that can be targeted by next-generation antimalarial interventions.
Databáze: MEDLINE