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PDBsum entry 6phc
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Immune system
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PDB id
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6phc
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Contents |
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158 a.a.
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228 a.a.
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217 a.a.
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PDB id:
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Immune system
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Title:
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Pfs25 in complex with the human transmission blocking antibody 2544
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Structure:
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25 kda ookinete surface antigen. Chain: i, e. Synonym: pfs25. Engineered: yes. 2544 antibody fab, heavy chain. Chain: a, c. Engineered: yes. 2544 antibody fab, light chain. Chain: b, d.
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Source:
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Plasmodium falciparum. Organism_taxid: 5833. Expressed in: homo sapiens. Expression_system_taxid: 9606. Homo sapiens. Human. Organism_taxid: 9606. Expression_system_taxid: 9606
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Resolution:
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2.90Å
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R-factor:
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0.202
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R-free:
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0.238
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Authors:
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B.R.Mcleod,J.P.Julien
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Key ref:
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B.McLeod
et al.
(2019).
Potent antibody lineage against malaria transmission elicited by human vaccination with Pfs25.
Nat Commun,
10,
4328.
PubMed id:
DOI:
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Date:
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25-Jun-19
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Release date:
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02-Oct-19
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PROCHECK
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Headers
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References
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P13829
(OS25_PLAFO) -
25 kDa ookinete surface antigen from Plasmodium falciparum (isolate NF54)
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Seq:
Struc:
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217 a.a.
158 a.a.*
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DOI no:
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Nat Commun
10:4328
(2019)
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PubMed id:
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Potent antibody lineage against malaria transmission elicited by human vaccination with Pfs25.
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B.McLeod,
K.Miura,
S.W.Scally,
A.Bosch,
N.Nguyen,
H.Shin,
D.Kim,
W.Volkmuth,
S.Rämisch,
J.A.Chichester,
S.Streatfield,
C.Woods,
W.R.Schief,
D.Emerling,
C.R.King,
J.P.Julien.
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ABSTRACT
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Transmission-blocking vaccines have the potential to be key contributors to
malaria elimination. Such vaccines elicit antibodies that inhibit parasites
during their development in Anopheles mosquitoes, thus breaking the cycle of
transmission. To date, characterization of humoral responses to Plasmodium
falciparum transmission-blocking vaccine candidate Pfs25 has largely been
conducted in pre-clinical models. Here, we present molecular analyses of human
antibody responses generated in a clinical trial evaluating Pfs25 vaccination.
From a collection of monoclonal antibodies with transmission-blocking activity,
we identify the most potent transmission-blocking antibody yet described against
Pfs25; 2544. The interactions of 2544 and three other antibodies with Pfs25 are
analyzed by crystallography to understand structural requirements for
elicitation of human transmission-blocking responses. Our analyses provide
insights into Pfs25 immunogenicity and epitope potency, and detail an affinity
maturation pathway for a potent transmission-blocking antibody in humans. Our
findings can be employed to guide the design of improved malaria
transmission-blocking vaccines.
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Links
