Application of replication-defective West Nile virus vector to non-flavivirus vaccine targets

Autor: Timothy Farrell, Irina V. Ustyugova, Konstantin V. Pugachev, Michael Vaine, Thorsten U. Vogel, Sanjay Phogat, Maryann Giel-Moloney, Svetlana Pougatcheva, Linong Zhang, Beata Gajewska, Xiaochu Duan, Mark Parrington, Harry Kleanthous
Rok vydání: 2017
Předmět:
0301 basic medicine
vaccine vector
T-Lymphocytes
viruses
Genetic Vectors
Immunology
Orthomyxoviridae
Cytomegalovirus
Gene Expression
Hemagglutinin Glycoproteins
Influenza Virus
Antibodies
Viral
Virus Replication
medicine.disease_cause
Defective virus
Virus
03 medical and health sciences
0302 clinical medicine
Viral Envelope Proteins
preclinical
medicine
Animals
Immunology and Allergy
030212 general & internal medicine
Vector (molecular biology)
Pharmacology
Drug Carriers
Mice
Inbred BALB C
Vaccines
Synthetic
biology
Viral Vaccine
Defective Viruses
non-flavivirus target
virus diseases
Viral Vaccines
T-Lymphocytes
Helper-Inducer
Simian immunodeficiency virus
biology.organism_classification
Research Papers
Virology
replication-defective
Flavivirus
030104 developmental biology
Viral replication
RepliVax
Simian Immunodeficiency Virus
Viral Fusion Proteins
West Nile virus
Zdroj: Human Vaccines & Immunotherapeutics
ISSN: 2164-554X
2164-5515
Popis: The RepliVax vaccine platform(RV) is based on flavivirus genomes that are rationally attenuated by deletion. The self-limiting infection provided by RV has been demonstrated to be safe, highly immunogenic and efficacious for several vaccine candidates against flaviviruses. Here respiratory syncytial virus (RSV) F, influenza virus HA, and simian immunodeficiency virus (SIV) Env proteins were expressed in place of either prM-E or C-prM-E gene deletions of the West Nile (WN) virus genome. The resulting RV-RSV, -influenza and -SIV vaccine prototypes replicated efficiently in complementing helper cells expressing the WN structural proteins in trans. Expressed antigens exhibited correct post-translational processing and the RV recombinants were shown to be highly attenuated and immunogenic in mice, eliciting strong antigen-specific antibodies as well as detectable T-cell responses. These data support the utility of RV vectors for development of vaccines against non-flavivirus targets including rabies and HIV.
Databáze: OpenAIRE
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