A humanized monoclonal antibody targeting protein a promotes opsonophagocytosis of Staphylococcus aureus in human umbilical cord blood.
Antibody-mediated opsonophagocytosis
Monoclonal antibody
Neonatal bacteremia/meningitis
Staphylococcal protein A
Staphylococcus aureus
Umbilical cord blood
Journal
Vaccine
ISSN: 1873-2518
Titre abrégé: Vaccine
Pays: Netherlands
ID NLM: 8406899
Informations de publication
Date de publication:
07 08 2023
07 08 2023
Historique:
received:
20
03
2023
revised:
03
06
2023
accepted:
09
07
2023
medline:
7
8
2023
pubmed:
17
7
2023
entrez:
16
7
2023
Statut:
ppublish
Résumé
Low and very-low-birth-weight (V/LBW) neonates are highly susceptible to bacterial sepsis and meningitis. Bacterial infections caused by Staphylococcus aureus can be particularly dangerous for neonates and can result in high mortality and long-term disabilities.Antibody-based strategies have been attempted to protect V/LBW neonates against staphylococcal disease. However, these efforts have so far been unsuccessful. Failures were attributed to the immaturity of the neonatal immune system but did not account for the anti-opsonic activity of Staphylococcal protein A (SpA). Here we show that monoclonal antibody 3F6, which blocks SpA activity, promotes complement-dependent cell-mediated phagocytosis of S. aureus in human umbilical cord blood. A substitution in the crystallizable fragment (Fc) region of 3F6 that enhances recruitment of complement component C1q further increases the phagocytic activity of cord blood. Our data demonstrate that the neonatal immune system possesses bactericidal activity that can be harnessed by antibodies that circumvent a key innate immune strategy of S. aureus.
Identifiants
pubmed: 37455161
pii: S0264-410X(23)00830-7
doi: 10.1016/j.vaccine.2023.07.018
pmc: PMC10412981
pii:
doi:
Substances chimiques
Staphylococcal Protein A
0
Antibodies, Bacterial
0
Antibodies, Monoclonal, Humanized
0
Antibodies, Monoclonal
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5079-5084Subventions
Organisme : NIAID NIH HHS
ID : R01 AI148543
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014599
Pays : United States
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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