Vaccination with a structure-based stabilized version of malarial antigen Pfs48/45 elicits ultra-potent transmission-blocking antibody responses.
antibodies
malaria
structure-based immunogen design
Journal
Immunity
ISSN: 1097-4180
Titre abrégé: Immunity
Pays: United States
ID NLM: 9432918
Informations de publication
Date de publication:
13 09 2022
13 09 2022
Historique:
received:
12
05
2022
revised:
07
07
2022
accepted:
18
07
2022
pubmed:
18
8
2022
medline:
17
9
2022
entrez:
17
8
2022
Statut:
ppublish
Résumé
Malaria transmission-blocking vaccines (TBVs) aim to elicit human antibodies that inhibit sporogonic development of Plasmodium falciparum in mosquitoes, thereby preventing onward transmission. Pfs48/45 is a leading clinical TBV candidate antigen and is recognized by the most potent transmission-blocking monoclonal antibody (mAb) yet described; still, clinical development of Pfs48/45 antigens has been hindered, largely by its poor biochemical characteristics. Here, we used structure-based computational approaches to design Pfs48/45 antigens stabilized in the conformation recognized by the most potently inhibitory mAb, achieving >25°C higher thermostability compared with the wild-type protein. Antibodies elicited in mice immunized with these engineered antigens displayed on liposome-based or protein nanoparticle-based vaccine platforms exhibited 1-2 orders of magnitude superior transmission-reducing activity, compared with immunogens bearing the wild-type antigen, driven by improved antibody quality. Our data provide the founding principles for using molecular stabilization solely from antibody structure-function information to drive improved immune responses against a parasitic vaccine target.
Identifiants
pubmed: 35977542
pii: S1074-7613(22)00350-8
doi: 10.1016/j.immuni.2022.07.015
pmc: PMC9487866
pii:
doi:
Substances chimiques
Antibodies, Blocking
0
Antibodies, Monoclonal
0
Antibodies, Protozoan
0
Antigens, Protozoan
0
Malaria Vaccines
0
Membrane Glycoproteins
0
Protozoan Proteins
0
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1680-1692.e8Subventions
Organisme : NIAID NIH HHS
ID : R01 AI148557
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007750
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests. A patent application has been filed that relates to this work.
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