Adjuvanted rabies vaccine with improved viscosity profile
Inventors
Maki, Joanne L. • Fry, Tricia Lynn • Hurley, Jerome Cornelius • Miller, Lowell Allen
Assignees
US Department of Agriculture USDA • Boehringer Ingelheim Animal Health USA Inc
Publication Number
US-9216213-B2
Publication Date
2015-12-22
Expiration Date
2032-04-20
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Abstract
The present invention relates to adjuvanted recombinant anti-rabies vaccines and the oral administration of such vaccines to raccoons and other wildlife. Advantageously, the anti-rabies vaccine may comprise a recombinant vaccinia virus containing a rabies glycoprotein gene. The invention encompasses methods of vaccinating raccoons and other wildlife by administration of an anti-rabies vaccines which may comprise a recombinant vaccinia virus containing a rabies glycoprotein gene, in combination with an adjuvant which increases both vaccine viscosity and efficacy. The invention provides effective oral recombinant vaccines used in oral rabies vaccination (ORV) programs for wildlife, effective at protecting raccoons, gray foxes, coyotes, and other animals.
Core Innovation
The invention relates to adjuvanted recombinant anti-rabies vaccines, specifically oral administration of such vaccines to raccoons and other wildlife. It involves an anti-rabies vaccine comprising a recombinant vaccinia virus containing a rabies glycoprotein gene combined with an adjuvant that increases both vaccine viscosity and efficacy. The invention aims to provide effective oral recombinant vaccines used in oral rabies vaccination (ORV) programs for wildlife such as raccoons, gray foxes, and coyotes.
The problem being solved is the suboptimal vaccination of wildlife against rabies due to limitations of current oral vaccines like RABORAL V-RG®, which is delivered in a liquid form prone to spillage or rejection by animals, reducing the effective dose ingested. Additionally, oral rabies vaccination programs (ORV) achieve only about 30% vaccination rates in raccoons, below the estimated 70% threshold to break disease transmission cycles. There is a need for an adjuvanted vaccine bait that is safe, inexpensive, easy to formulate, more viscous to reduce vaccine loss, and stable in environmental conditions to increase vaccination efficacy and coverage in wildlife populations.
The invention unexpectedly demonstrates that formulating RABORAL V-RG® with specific variants of chitosan, particularly trimethylated chitosan (TMC), improves oral vaccine efficacy by enhancing immune response and increasing vaccine viscosity. This increased viscosity reduces spillage during administration, overcoming limitations of current liquid formulations. The invention also includes methods for screening candidate adjuvants in vitro to select those that do not have virucidal effects detrimental to vaccine vectors before progressing to animal studies.
Claims Coverage
The claims comprise one composition claim and several method claims, describing the adjuvanted rabies vaccine composition and methods of eliciting protective immune responses with it. The main inventive features include the composition of the vaccine with a viral vector and trimethylated chitosan adjuvant and the method of use in animals.
Single-dose adjuvanted rabies vaccine composition
A vaccine composition comprising an attenuated recombinant Orthopox or Avipox viral vector expressing a full-length G protein from the ERA rabies strain, combined with about 2.5% w/v trimethylated chitosan (TMC) as an adjuvant. The adjuvant increases both vaccine viscosity and protective efficacy compared to compositions without the adjuvant, eliciting protective rabies virus neutralizing antibodies in at least 90% of animals within 90 days after a single dose.
Oral vaccine formulation and vector variants
The vaccine composition may be administered orally. The viral vector may be an Avipox virus or a Vaccinia virus, including variants such as the Copenhagen strain and tk− phenotype of Vaccinia virus.
Method of eliciting protective immune response in animals
A method of eliciting a protective immune response against rabies virus in an animal by administering a single effective dose of the described composition, wherein the viral vector may be an attenuated Vaccinia virus (e.g., Copenhagen strain, tk− phenotype), administered orally, optionally by bait drop, and applied to animals including raccoons.
The claims define the invention as a single-dose oral rabies vaccine composition comprising a recombinant viral vector and TMC adjuvant that increases viscosity and protective efficacy, and methods of immunizing animals against rabies using this composition to achieve improved immune responses.
Stated Advantages
The vaccine adjuvant increases vaccine viscosity which reduces vaccine spillage and loss during oral administration in wildlife, improving effective dose consumption.
The adjuvanted vaccine improves protective efficacy, eliciting protective neutralizing antibody responses in a higher proportion of animals after a single dose, including raccoons.
The vaccine bait is safe, inexpensive, easy to formulate, and environmentally stable for use in wildlife oral rabies vaccination programs.
Documented Applications
Oral vaccination of wildlife animals such as raccoons, gray foxes, coyotes, skunks, and mongooses against rabies virus.
Use in oral rabies vaccination (ORV) programs for controlling and eventually eliminating terrestrial rabies in wildlife populations.
Administration via oral routes including bait drops comprising hollow polymer cubes or coated sachets that release the vaccine in the animal's mouth.
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