Efficient oral vaccination by bioengineering virus-like particles with protozoan surface proteins.
Adjuvants, Immunologic
Administration, Oral
Animals
Antigen Presentation
/ drug effects
Bioengineering
/ methods
Dendritic Cells
/ drug effects
Female
Gene Expression
Giardia lamblia
/ chemistry
Hemagglutinin Glycoproteins, Influenza Virus
/ genetics
Humans
Immunity, Innate
/ drug effects
Influenza Vaccines
/ administration & dosage
Male
Membrane Proteins
/ genetics
Mice
Mice, Transgenic
Neuraminidase
/ genetics
Orthomyxoviridae Infections
/ immunology
Protein Stability
Protozoan Proteins
/ genetics
Toll-Like Receptor 4
/ genetics
Trophozoites
/ chemistry
Vaccination
Vaccines, Virus-Like Particle
/ administration & dosage
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
21 01 2019
21 01 2019
Historique:
received:
02
08
2018
accepted:
22
12
2018
entrez:
22
1
2019
pubmed:
22
1
2019
medline:
6
2
2019
Statut:
epublish
Résumé
Intestinal and free-living protozoa, such as Giardia lamblia, express a dense coat of variant-specific surface proteins (VSPs) on trophozoites that protects the parasite inside the host's intestine. Here we show that VSPs not only are resistant to proteolytic digestion and extreme pH and temperatures but also stimulate host innate immune responses in a TLR-4 dependent manner. We show that these properties can be exploited to both protect and adjuvant vaccine antigens for oral administration. Chimeric Virus-like Particles (VLPs) decorated with VSPs and expressing model surface antigens, such as influenza virus hemagglutinin (HA) and neuraminidase (NA), are protected from degradation and activate antigen presenting cells in vitro. Orally administered VSP-pseudotyped VLPs, but not plain VLPs, generate robust immune responses that protect mice from influenza infection and HA-expressing tumors. This versatile vaccine platform has the attributes to meet the ultimate challenge of generating safe, stable and efficient oral vaccines.
Identifiants
pubmed: 30664644
doi: 10.1038/s41467-018-08265-9
pii: 10.1038/s41467-018-08265-9
pmc: PMC6341118
doi:
Substances chimiques
Adjuvants, Immunologic
0
Hemagglutinin Glycoproteins, Influenza Virus
0
Influenza Vaccines
0
Membrane Proteins
0
Protozoan Proteins
0
Tlr4 protein, mouse
0
Toll-Like Receptor 4
0
Vaccines, Virus-Like Particle
0
hemagglutinin, human influenza A virus
0
Neuraminidase
EC 3.2.1.18
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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