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US 11,628,213 B2Granted
Ichthyophthirius multifiliis vaccine system
AssigneeUniversity of Florida Research Foundation, Inc.
InventorsRoy Curtiss, III, Banikalyan Swain
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AssigneeUniversity of Florida Research Foundation, Inc.
InventorsRoy Curtiss, III, Banikalyan Swain
Estimating the term…
Disclosed herein are nucleic acids, vector systems, and vaccines for vaccinating fresh water and marine fish using Ichthyophthirius multifiliis (Ich) i-antigens. In particular, a recombinant attenuated Edwardsiella vaccine (RAEV) vector system is disclosed with regulated delayed attenuation and regulated delayed lysis in vivo attributes that synthesizes Ich protective antigens to enable vaccination of fresh water and marine fish species susceptible to white spot disease. This vaccine construct is designed to exhibit the invasive properties of virulent Edwardsiella at the time of bath immunization and then is programmed to gradually lose virulence attributes and to synthesize protective antigens as a consequence of in vivo cell division as the RAEV colonizes internal effector lymphoid tissues. The ultimate lysis in vivo delivers a bolus of protective antigen along with immunostimulatory molecules to exhibit complete biological containment with no potential for survival in vivo or ex vivo.
A genetically modified antibiotic-sensitive recombinant derivative of the piscine-restricted Gram-negative Edwardsiella piscicida capable of invasion into, or infecting, marine and fresh-water fish species that displays:
A genetically modified Edwardsiella piscicida bacterium displaying a regulated delayed manifestation of attenuation in vivo, able to synthesize and deliver protective antigens encoded by genes from heterologous pathogens and capable of infecting fresh water and marine fish to deliver such synthesized protective antigens,
A genetically modified Edwardsiella piscicida bacterium displaying a balanced-lethal vector-host phenotype wherein the bacterium possesses one or more chromosomal mutations that would preclude synthesis of essential unique constituents of the peptidoglycan layer of the bacterial cell wall under non-permissive in vivo conditions and a plasmid vector that possesses regulatable genes to complement the chromosomal mutations but cease to do so under non-permissive in vivo conditions leading to death by lysis.
A genetically modified antibiotic-sensitive recombinant derivative of the piscine-restricted gram-negative Edwardsiella piscicida bacterium capable of invasion into or infecting marine and fresh-water fish species that displays (i) a regulated delayed manifestation of attenuation in vivo wherein the bacterium comprises a chromosomally integrated regulatable promoter operably linked to a nucleic acid sequence encoding an attenuation protein such that transcription of the nucleic acid sequence encoding the attenuation protein occurs in a permissive environment, but ceases in a non-permissive in vivo environment, (ii) a regulated delayed expression in vivo of at least one heterologous codon-optimized nucleic acid sequence encoding an antigen wherein the bacterium comprises at least one chromosomally integrated nucleic acid sequence encoding a repressor operably linked to a regulatable promoter, and an extra-chromosomal plasmid vector comprising at least one nucleic acid sequence encoding a protective antigen operably linked to a promoter regulated by the repressor, such that the expression of the nucleic acid sequence encoding the antigen is repressed during in vitro growth of the bacterium, but the bacterium is capable of high level expression in vivo, and (iii) a regulated delayed lysis in vivo phenotype that constitutes a balanced-lethal vector-host to confer biological containment wherein the bacterium is able to synthesize components of the peptidoglycan cell wall layer under permissive conditions and unable to do so under non-permissive in vivo conditions.
Dependencies are inferred from the claim text.