Potent tetravalent replicon vaccines against botulinum neurotoxins using DNA-based Semliki Forest virus replicon vectors. 2013

Yun-Zhou Yu, and Jin-Peng Guo, and Huai-Jie An, and Shu-Ming Zhang, and Shuang Wang, and Wei-Yuan Yu, and Zhi-Wei Sun
Beijing Institute of Biotechnology, Beijing, China. yunzhouyu@163.com

Human botulism is commonly associated with botulinum neurotoxin (BoNT) serotypes A, B, E and F. This suggests that the greatest need is for a tetravalent vaccine that provides protection against all four of these serotypes. In current study, we investigated the feasibility of generating several tetravalent vaccines that protected mice against the four serotypes. Firstly, monovalent replicon vaccine against BoNT induced better antibody response and protection than that of corresponding conventional DNA vaccine. Secondly, dual-expression DNA replicon pSCARSE/FHc or replicon particle VRP-E/FHc vaccine was well resistant to the challenge of BoNT/E and BoNT/F mixture as a combination vaccine composed of two monovalent replicon vaccines. Finally, the dual-expression DNA replicon or replicon particle tetravalent vaccine could simultaneously and effectively neutralize and protect the four BoNT serotypes. Protection correlated directly with serum ELISA titers and neutralization antibody levels to BoNTs. Therefore, replicon-based DNA or particle might be effective vector to develop BoNT vaccines, which might be more desirable for use in clinical application than the conventional DNA vaccines. Our studies demonstrate the utility of combining dual-expression DNA replicon or replicon particle vaccines into multi-agent formulations as potent tetravalent vaccines for eliciting protective responses to four serotypes of BoNTs.

UI MeSH Term Description Entries
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D009498 Neurotoxins Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept. Alpha-Neurotoxin,Excitatory Neurotoxin,Excitotoxins,Myotoxin,Myotoxins,Neurotoxin,Alpha-Neurotoxins,Excitatory Neurotoxins,Excitotoxin,Alpha Neurotoxin,Alpha Neurotoxins,Neurotoxin, Excitatory,Neurotoxins, Excitatory
D012093 Replicon Any DNA sequence capable of independent replication or a molecule that possesses a REPLICATION ORIGIN and which is therefore potentially capable of being replicated in a suitable cell. (Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed) Replication Unit,Replication Units,Replicons,Unit, Replication,Units, Replication
D001905 Botulinum Toxins Toxic proteins produced from the species CLOSTRIDIUM BOTULINUM. The toxins are synthesized as a single peptide chain which is processed into a mature protein consisting of a heavy chain and light chain joined via a disulfide bond. The botulinum toxin light chain is a zinc-dependent protease which is released from the heavy chain upon ENDOCYTOSIS into PRESYNAPTIC NERVE ENDINGS. Once inside the cell the botulinum toxin light chain cleaves specific SNARE proteins which are essential for secretion of ACETYLCHOLINE by SYNAPTIC VESICLES. This inhibition of acetylcholine release results in muscular PARALYSIS. Botulin,Botulinum Neurotoxin,Botulinum Neurotoxins,Clostridium botulinum Toxins,Botulinum Toxin,Neurotoxin, Botulinum,Neurotoxins, Botulinum,Toxin, Botulinum,Toxins, Botulinum,Toxins, Clostridium botulinum
D001906 Botulism A disease caused by potent protein NEUROTOXINS produced by CLOSTRIDIUM BOTULINUM which interfere with the presynaptic release of ACETYLCHOLINE at the NEUROMUSCULAR JUNCTION. Clinical features include abdominal pain, vomiting, acute PARALYSIS (including respiratory paralysis), blurred vision, and DIPLOPIA. Botulism may be classified into several subtypes (e.g., food-borne, infant, wound, and others). (From Adams et al., Principles of Neurology, 6th ed, p1208) Botulism, Infantile,Botulism, Toxico-Infectious,Clostridium botulinum Infection,Foodborne Botulism,Infant Botulism,Toxico-Infectious Botulism,Wound Botulism,Botulism, Foodborne,Botulism, Infant,Botulism, Toxico Infectious,Botulism, Wound,Clostridium botulinum Infections,Foodborne Botulisms,Infant Botulisms,Infantile Botulism,Infection, Clostridium botulinum,Toxico Infectious Botulism,Wound Botulisms
D003014 Clostridium botulinum A species of anaerobic, gram-positive, rod-shaped bacteria in the family Clostridiaceae that produces proteins with characteristic neurotoxicity. It is the etiologic agent of BOTULISM in humans, wild fowl, HORSES; and CATTLE. Seven subtypes (sometimes called antigenic types, or strains) exist, each producing a different botulinum toxin (BOTULINUM TOXINS). The organism and its spores are widely distributed in nature.
D004797 Enzyme-Linked Immunosorbent Assay An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. ELISA,Assay, Enzyme-Linked Immunosorbent,Assays, Enzyme-Linked Immunosorbent,Enzyme Linked Immunosorbent Assay,Enzyme-Linked Immunosorbent Assays,Immunosorbent Assay, Enzyme-Linked,Immunosorbent Assays, Enzyme-Linked
D005260 Female Females
D005822 Genetic Vectors DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition. Cloning Vectors,Shuttle Vectors,Vectors, Genetic,Cloning Vector,Genetic Vector,Shuttle Vector,Vector, Cloning,Vector, Genetic,Vector, Shuttle,Vectors, Cloning,Vectors, Shuttle
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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