Back to Search
Start Over
Vaccine display on artificial bacterial spores enhances protective efficacy against Staphylococcus aureus infection
- Source :
- FEMS Microbiology Letters. 365
- Publication Year :
- 2018
- Publisher :
- Oxford University Press (OUP), 2018.
-
Abstract
- Spores of Bacillus subtilis are encased in a protein coat composed of ∼80 different proteins. Recently, we reconstituted the basement layer of the coat, composed of two structural proteins (SpoVM and SpoIVA) around spore-sized silica beads encased in a lipid bilayer, to create synthetic spore-like particles termed ‘SSHELs’. We demonstrated that SSHELs could display thousands of copies of proteins and small molecules of interest covalently linked to SpoIVA. In this study, we investigated the efficacy of SSHELs in delivering vaccines. We show that intramuscular vaccination of mice with undecorated one micron-diameter SSHELs elicited an antibody response against SpoIVA. We further demonstrate that SSHELs covalently modified with a catalytically inactivated staphylococcal alpha toxin variant (Hla(H35L)), without an adjuvant, resulted in improved protection against Staphylococcus aureus infection in a bacteremia model as compared to vaccination with the antigen alone. Although vaccination with either Hla(H35L) or Hla(H35L) conjugated to SSHELs similarly elicited the production of neutralizing antibodies to Hla, we found that a subset of memory T cells was differentially activated when the antigen was delivered on SSHELs. We propose that the particulate nature of SSHELs elicits a more robust immune response to the vaccine that results in superior protection against subsequent S. aureus infection.
- Subjects :
- 0301 basic medicine
Recombinant Fusion Proteins
medicine.medical_treatment
Bacterial Toxins
Bacteremia
Human leukocyte antigen
Bacillus subtilis
medicine.disease_cause
Injections, Intramuscular
Microbiology
Hemolysin Proteins
Mice
03 medical and health sciences
Immune system
Bacterial Proteins
Antigen
T-Lymphocyte Subsets
Research Letter
Genetics
medicine
Animals
Molecular Biology
Drug Carriers
Vaccines, Synthetic
biology
Chemistry
Staphylococcal Vaccines
Staphylococcal Infections
biology.organism_classification
Antibodies, Bacterial
Antibodies, Neutralizing
Vaccination
Disease Models, Animal
Treatment Outcome
030104 developmental biology
Staphylococcus aureus
Vaccines, Subunit
biology.protein
Antibody
Adjuvant
Subjects
Details
- ISSN :
- 15746968
- Volume :
- 365
- Database :
- OpenAIRE
- Journal :
- FEMS Microbiology Letters
- Accession number :
- edsair.doi.dedup.....f10a96f4a5a896326e25333124922248