Your browser doesn't support javascript.
loading
Vaccination in a humanized mouse model elicits highly protective PfCSP-targeting anti-malarial antibodies.
Kratochvil, Sven; Shen, Chen-Hsiang; Lin, Ying-Cing; Xu, Kai; Nair, Usha; Da Silva Pereira, Lais; Tripathi, Prabhanshu; Arnold, Johan; Chuang, Gwo-Yu; Melzi, Eleonora; Schön, Arne; Zhang, Baoshan; Dillon, Marlon; Bonilla, Brian; Flynn, Barbara J; Kirsch, Kathrin H; Kisalu, Neville K; Kiyuka, Patience K; Liu, Tracy; Ou, Li; Pancera, Marie; Rawi, Reda; Reveiz, Mateo; Seignon, Kareen; Wang, Lawrence T; Waring, Michael T; Warner, John; Yang, Yongping; Francica, Joseph R; Idris, Azza H; Seder, Robert A; Kwong, Peter D; Batista, Facundo D.
Affiliation
  • Kratochvil S; The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
  • Shen CH; Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
  • Lin YC; The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
  • Xu K; Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
  • Nair U; The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
  • Da Silva Pereira L; Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
  • Tripathi P; Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
  • Arnold J; The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
  • Chuang GY; Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
  • Melzi E; The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
  • Schön A; Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Zhang B; Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
  • Dillon M; Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
  • Bonilla B; Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
  • Flynn BJ; Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
  • Kirsch KH; The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
  • Kisalu NK; Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
  • Kiyuka PK; Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
  • Liu T; Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
  • Ou L; Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
  • Pancera M; Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA; Vaccine Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Rawi R; Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
  • Reveiz M; Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
  • Seignon K; The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
  • Wang LT; Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
  • Waring MT; The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
  • Warner J; The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
  • Yang Y; Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
  • Francica JR; Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
  • Idris AH; The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA; Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
  • Seder RA; Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: rseder@nih.gov.
  • Kwong PD; Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: pdkwong@nih.gov.
  • Batista FD; The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA; Department of Immunology, Harvard Medical School, Boston, MA, USA; Department of Microbiology, Harvard Medical School, Boston, MA, USA. Electronic address: fbatist
Immunity ; 54(12): 2859-2876.e7, 2021 12 14.
Article de En | MEDLINE | ID: mdl-34788599
ABSTRACT
Repeat antigens, such as the Plasmodium falciparum circumsporozoite protein (PfCSP), use both sequence degeneracy and structural diversity to evade the immune response. A few PfCSP-directed antibodies have been identified that are effective at preventing malaria infection, including CIS43, but how these repeat-targeting antibodies might be improved has been unclear. Here, we engineered a humanized mouse model in which B cells expressed inferred human germline CIS43 (iGL-CIS43) B cell receptors and used both vaccination and bioinformatic analysis to obtain variant CIS43 antibodies with improved protective capacity. One such antibody, iGL-CIS43.D3, was significantly more potent than the current best-in-class PfCSP-directed antibody. We found that vaccination with a junctional epitope peptide was more effective than full-length PfCSP at recruiting iGL-CIS43 B cells to germinal centers. Structure-function analysis revealed multiple somatic hypermutations that combinatorically improved protection. This mouse model can thus be used to understand vaccine immunogens and to develop highly potent anti-malarial antibodies.
Sujet(s)
Mots clés
Texte intégral
Ajouter à My VHL
Imprimer
XML
PubMed Links
Recherche sur Google

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Plasmodium falciparum / Protéines de protozoaire / Sous-populations de lymphocytes B / Vaccins contre le paludisme / Vaccins à ADN / Paludisme / Épitopes Limites: Animals / Humans Langue: En Journal: Immunity Sujet du journal: ALERGIA E IMUNOLOGIA Année: 2021 Type de document: Article Pays d'affiliation: États-Unis d'Amérique
Texte intégral
Ajouter à My VHL
Imprimer
XML
PubMed Links
Recherche sur Google

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Plasmodium falciparum / Protéines de protozoaire / Sous-populations de lymphocytes B / Vaccins contre le paludisme / Vaccins à ADN / Paludisme / Épitopes Limites: Animals / Humans Langue: En Journal: Immunity Sujet du journal: ALERGIA E IMUNOLOGIA Année: 2021 Type de document: Article Pays d'affiliation: États-Unis d'Amérique