Heterotypic interactions drive antibody synergy against a malaria vaccine candidate.
Animals
Antibodies, Monoclonal
/ immunology
Antibodies, Protozoan
/ immunology
Antigens, Protozoan
/ genetics
Cell Line
Drosophila melanogaster
Epitopes
/ immunology
Humans
Immunogenicity, Vaccine
Malaria Vaccines
/ immunology
Malaria, Falciparum
/ immunology
Plasmodium falciparum
/ immunology
Protozoan Proteins
/ genetics
Vaccine Development
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
17 02 2022
17 02 2022
Historique:
received:
11
11
2021
accepted:
29
01
2022
entrez:
18
2
2022
pubmed:
19
2
2022
medline:
4
3
2022
Statut:
epublish
Résumé
Understanding mechanisms of antibody synergy is important for vaccine design and antibody cocktail development. Examples of synergy between antibodies are well-documented, but the mechanisms underlying these relationships often remain poorly understood. The leading blood-stage malaria vaccine candidate, CyRPA, is essential for invasion of Plasmodium falciparum into human erythrocytes. Here we present a panel of anti-CyRPA monoclonal antibodies that strongly inhibit parasite growth in in vitro assays. Structural studies show that growth-inhibitory antibodies bind epitopes on a single face of CyRPA. We also show that pairs of non-competing inhibitory antibodies have strongly synergistic growth-inhibitory activity. These antibodies bind to neighbouring epitopes on CyRPA and form lateral, heterotypic interactions which slow antibody dissociation. We predict that such heterotypic interactions will be a feature of many immune responses. Immunogens which elicit such synergistic antibody mixtures could increase the potency of vaccine-elicited responses to provide robust and long-lived immunity against challenging disease targets.
Identifiants
pubmed: 35177602
doi: 10.1038/s41467-022-28601-4
pii: 10.1038/s41467-022-28601-4
pmc: PMC8854392
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Protozoan
0
Antigens, Protozoan
0
CyRPA protein, Plasmodium falciparum
0
Epitopes
0
Malaria Vaccines
0
Protozoan Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
933Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 106917/Z/15/Z
Pays : United Kingdom
Organisme : CIHR
ID : FRN:157835
Pays : Canada
Organisme : Wellcome Trust (Wellcome)
ID : 220797/Z/20/Z
Informations de copyright
© 2022. The Author(s).
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