Cargando…
A human monoclonal antibody prevents malaria infection and defines a new site of vulnerability on Plasmodium falciparum circumsporozoite protein
Development of a highly effective vaccine or antibodies for prevention and ultimately elimination of malaria is urgently needed. Here, we report the isolation of a number of human monoclonal antibodies (mAbs) directed against the Plasmodium falciparum (Pf) circumsporozoite protein (CSP) from several...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5893371/ https://www.ncbi.nlm.nih.gov/pubmed/29554083 http://dx.doi.org/10.1038/nm.4512 |
_version_ | 1783313298787139584 |
---|---|
author | Kisalu, Neville K. Idris, Azza H. Weidle, Connor Flores-Garcia, Yevel Flynn, Barbara J. Sack, Brandon K. Murphy, Sean Schön, Arne Freire, Ernesto Francica, Joseph R. Miller, Alex B. Gregory, Jason March, Sandra Liao, Hua-Xin Haynes, Barton F. Wiehe, Kevin Trama, Ashley M. Saunders, Kevin O. Gladden, Morgan A. Monroe, Anthony Bonsignori, Mattia Kanekiyo, Masaru Wheatley, Adam K. McDermott, Adrian B. Farney, S. Katie Chuang, Gwo-Yu Zhang, Baoshan Natasha, K C Chakravarty, Sumana Kwong, Peter D. Sinnis, Photini Bhatia, Sangeeta N. Kappe, Stefan H. I. Sim, B. Kim Lee Hoffman, Stephen L. Zavala, Fidel Pancera, Marie Seder, Robert A. |
author_facet | Kisalu, Neville K. Idris, Azza H. Weidle, Connor Flores-Garcia, Yevel Flynn, Barbara J. Sack, Brandon K. Murphy, Sean Schön, Arne Freire, Ernesto Francica, Joseph R. Miller, Alex B. Gregory, Jason March, Sandra Liao, Hua-Xin Haynes, Barton F. Wiehe, Kevin Trama, Ashley M. Saunders, Kevin O. Gladden, Morgan A. Monroe, Anthony Bonsignori, Mattia Kanekiyo, Masaru Wheatley, Adam K. McDermott, Adrian B. Farney, S. Katie Chuang, Gwo-Yu Zhang, Baoshan Natasha, K C Chakravarty, Sumana Kwong, Peter D. Sinnis, Photini Bhatia, Sangeeta N. Kappe, Stefan H. I. Sim, B. Kim Lee Hoffman, Stephen L. Zavala, Fidel Pancera, Marie Seder, Robert A. |
author_sort | Kisalu, Neville K. |
collection | PubMed |
description | Development of a highly effective vaccine or antibodies for prevention and ultimately elimination of malaria is urgently needed. Here, we report the isolation of a number of human monoclonal antibodies (mAbs) directed against the Plasmodium falciparum (Pf) circumsporozoite protein (CSP) from several subjects immunized with an attenuated whole sporozoite (SPZ) vaccine (Sanaria(®) PfSPZ Vaccine). Passive transfer of one of these antibodies, mAb CIS43, conferred high-level, sterile protection in two different mouse models of malaria infection. Stoichiometry and affinity of mAb CIS43 for PfCSP indicate two sequential multivalent binding events to six sites: the first 7-fold higher affinity binding event is to a unique “junctional” epitope positioned between the N-terminus and the central repeat domain of PfCSP. Moreover, mAb CIS43 prevented proteolytic cleavage of PfCSP on PfSPZ. Crystal structures of the CIS43 fragment antigen binding (Fab) in complex with the junctional epitope determined the molecular interactions of binding, revealed the epitope’s conformational flexibility, and defined NPN as the structural repeat motif. The demonstration that mAb CIS43 is highly effective for passive prevention of malaria has potential application for use in travelers, military personnel and elimination campaigns and identifies a new and conserved site of vulnerability on PfCSP for next generation rational vaccine design. |
format | Online Article Text |
id | pubmed-5893371 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
record_format | MEDLINE/PubMed |
spelling | pubmed-58933712018-09-19 A human monoclonal antibody prevents malaria infection and defines a new site of vulnerability on Plasmodium falciparum circumsporozoite protein Kisalu, Neville K. Idris, Azza H. Weidle, Connor Flores-Garcia, Yevel Flynn, Barbara J. Sack, Brandon K. Murphy, Sean Schön, Arne Freire, Ernesto Francica, Joseph R. Miller, Alex B. Gregory, Jason March, Sandra Liao, Hua-Xin Haynes, Barton F. Wiehe, Kevin Trama, Ashley M. Saunders, Kevin O. Gladden, Morgan A. Monroe, Anthony Bonsignori, Mattia Kanekiyo, Masaru Wheatley, Adam K. McDermott, Adrian B. Farney, S. Katie Chuang, Gwo-Yu Zhang, Baoshan Natasha, K C Chakravarty, Sumana Kwong, Peter D. Sinnis, Photini Bhatia, Sangeeta N. Kappe, Stefan H. I. Sim, B. Kim Lee Hoffman, Stephen L. Zavala, Fidel Pancera, Marie Seder, Robert A. Nat Med Article Development of a highly effective vaccine or antibodies for prevention and ultimately elimination of malaria is urgently needed. Here, we report the isolation of a number of human monoclonal antibodies (mAbs) directed against the Plasmodium falciparum (Pf) circumsporozoite protein (CSP) from several subjects immunized with an attenuated whole sporozoite (SPZ) vaccine (Sanaria(®) PfSPZ Vaccine). Passive transfer of one of these antibodies, mAb CIS43, conferred high-level, sterile protection in two different mouse models of malaria infection. Stoichiometry and affinity of mAb CIS43 for PfCSP indicate two sequential multivalent binding events to six sites: the first 7-fold higher affinity binding event is to a unique “junctional” epitope positioned between the N-terminus and the central repeat domain of PfCSP. Moreover, mAb CIS43 prevented proteolytic cleavage of PfCSP on PfSPZ. Crystal structures of the CIS43 fragment antigen binding (Fab) in complex with the junctional epitope determined the molecular interactions of binding, revealed the epitope’s conformational flexibility, and defined NPN as the structural repeat motif. The demonstration that mAb CIS43 is highly effective for passive prevention of malaria has potential application for use in travelers, military personnel and elimination campaigns and identifies a new and conserved site of vulnerability on PfCSP for next generation rational vaccine design. 2018-03-19 2018-05 /pmc/articles/PMC5893371/ /pubmed/29554083 http://dx.doi.org/10.1038/nm.4512 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Kisalu, Neville K. Idris, Azza H. Weidle, Connor Flores-Garcia, Yevel Flynn, Barbara J. Sack, Brandon K. Murphy, Sean Schön, Arne Freire, Ernesto Francica, Joseph R. Miller, Alex B. Gregory, Jason March, Sandra Liao, Hua-Xin Haynes, Barton F. Wiehe, Kevin Trama, Ashley M. Saunders, Kevin O. Gladden, Morgan A. Monroe, Anthony Bonsignori, Mattia Kanekiyo, Masaru Wheatley, Adam K. McDermott, Adrian B. Farney, S. Katie Chuang, Gwo-Yu Zhang, Baoshan Natasha, K C Chakravarty, Sumana Kwong, Peter D. Sinnis, Photini Bhatia, Sangeeta N. Kappe, Stefan H. I. Sim, B. Kim Lee Hoffman, Stephen L. Zavala, Fidel Pancera, Marie Seder, Robert A. A human monoclonal antibody prevents malaria infection and defines a new site of vulnerability on Plasmodium falciparum circumsporozoite protein |
title | A human monoclonal antibody prevents malaria infection and defines a new site of vulnerability on Plasmodium falciparum circumsporozoite protein |
title_full | A human monoclonal antibody prevents malaria infection and defines a new site of vulnerability on Plasmodium falciparum circumsporozoite protein |
title_fullStr | A human monoclonal antibody prevents malaria infection and defines a new site of vulnerability on Plasmodium falciparum circumsporozoite protein |
title_full_unstemmed | A human monoclonal antibody prevents malaria infection and defines a new site of vulnerability on Plasmodium falciparum circumsporozoite protein |
title_short | A human monoclonal antibody prevents malaria infection and defines a new site of vulnerability on Plasmodium falciparum circumsporozoite protein |
title_sort | human monoclonal antibody prevents malaria infection and defines a new site of vulnerability on plasmodium falciparum circumsporozoite protein |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5893371/ https://www.ncbi.nlm.nih.gov/pubmed/29554083 http://dx.doi.org/10.1038/nm.4512 |
work_keys_str_mv | AT kisalunevillek ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT idrisazzah ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT weidleconnor ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT floresgarciayevel ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT flynnbarbaraj ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT sackbrandonk ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT murphysean ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT schonarne ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT freireernesto ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT francicajosephr ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT milleralexb ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT gregoryjason ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT marchsandra ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT liaohuaxin ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT haynesbartonf ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT wiehekevin ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT tramaashleym ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT saunderskevino ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT gladdenmorgana ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT monroeanthony ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT bonsignorimattia ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT kanekiyomasaru ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT wheatleyadamk ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT mcdermottadrianb ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT farneyskatie ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT chuanggwoyu ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT zhangbaoshan ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT natashakc ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT chakravartysumana ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT kwongpeterd ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT sinnisphotini ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT bhatiasangeetan ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT kappestefanhi ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT simbkimlee ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT hoffmanstephenl ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT zavalafidel ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT panceramarie ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT sederroberta ahumanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT kisalunevillek humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT idrisazzah humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT weidleconnor humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT floresgarciayevel humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT flynnbarbaraj humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT sackbrandonk humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT murphysean humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT schonarne humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT freireernesto humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT francicajosephr humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT milleralexb humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT gregoryjason humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT marchsandra humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT liaohuaxin humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT haynesbartonf humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT wiehekevin humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT tramaashleym humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT saunderskevino humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT gladdenmorgana humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT monroeanthony humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT bonsignorimattia humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT kanekiyomasaru humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT wheatleyadamk humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT mcdermottadrianb humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT farneyskatie humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT chuanggwoyu humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT zhangbaoshan humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT natashakc humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT chakravartysumana humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT kwongpeterd humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT sinnisphotini humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT bhatiasangeetan humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT kappestefanhi humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT simbkimlee humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT hoffmanstephenl humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT zavalafidel humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT panceramarie humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein AT sederroberta humanmonoclonalantibodypreventsmalariainfectionanddefinesanewsiteofvulnerabilityonplasmodiumfalciparumcircumsporozoiteprotein |