Broadly Protective Multivalent OspA Vaccine against Lyme Borreliosis, Developed Based on Surface Shaping of the C-Terminal Fragment.
Animals
Antigens, Surface
/ administration & dosage
Bacterial Outer Membrane Proteins
/ administration & dosage
Bacterial Vaccines
/ administration & dosage
Borrelia
/ genetics
Disease Models, Animal
Lipoproteins
/ administration & dosage
Lyme Disease
/ prevention & control
Mice
Protein Engineering
Recombinant Proteins
/ genetics
Vaccines, Synthetic
/ administration & dosage
Borrelia
Lyme
OspA
vaccine
Journal
Infection and immunity
ISSN: 1098-5522
Titre abrégé: Infect Immun
Pays: United States
ID NLM: 0246127
Informations de publication
Date de publication:
23 03 2020
23 03 2020
Historique:
received:
06
12
2019
accepted:
22
12
2019
pubmed:
15
1
2020
medline:
9
7
2020
entrez:
15
1
2020
Statut:
epublish
Résumé
The development of vaccines for prevention of diseases caused by pathogenic species can encounter major obstacles if high sequence diversity is observed between individual strains. Therefore, development might be restricted either to conserved antigens, which are often rare, or to multivalent vaccines, which renders the production more costly and cumbersome. In light of this complexity, we applied a structure-based surface shaping approach for the development of a Lyme borreliosis (LB) vaccine suitable for the United States and Europe. The surface of the C-terminal fragment of outer surface protein A (OspA) was divided into distinct regions, based primarily on binding sites of monoclonal antibodies (MAbs). In order to target the six clinically most relevant OspA serotypes (ST) in a single protein, exposed amino acids of the individual regions were exchanged to corresponding amino acids of a chosen OspA serotype. Six chimeric proteins were constructed, and, based on their immunogenicity, four of these chimeras were tested in mouse challenge models. Significant protection could be demonstrated for all four proteins following challenge with infected ticks (OspA ST1, OspA ST2, and OspA ST4) or with
Identifiants
pubmed: 31932330
pii: IAI.00917-19
doi: 10.1128/IAI.00917-19
pmc: PMC7093141
pii:
doi:
Substances chimiques
Antigens, Surface
0
Bacterial Outer Membrane Proteins
0
Bacterial Vaccines
0
Lipoproteins
0
OspA protein
0
Recombinant Proteins
0
Vaccines, Synthetic
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2020 American Society for Microbiology.
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