Leishmania vaccine using sand fly salivary immunogen
Inventors
Fischer, Laurent Bernard • Valenzuela, Jesus G. • Ribeiro, Jose • Kamhawi, Shaden
Assignees
MERIAL Ltd • Merial LLC • US Department of Health and Human Services
Publication Number
US-8603808-B2
Publication Date
2013-12-10
Expiration Date
2029-05-06
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Abstract
The present invention provides vectors that contain and express in vivo or in vitro sand fly Lu. longipalpis salivary antigens that elicit an immune response in animal or human against Leishmania, vaccine compositions comprising said vectors and/or Lu. longipalpis salivary polypeptides, methods of vaccination against Leishmania, and kits for use with such methods and compositions.
Core Innovation
The invention provides vectors that contain and express sand fly Lu. longipalpis salivary antigens that elicit an immune response in animals or humans against Leishmania. These include recombinant vectors, such as recombinant poxviruses, that express at least one exogenous nucleic acid encoding immunogens or epitopes derived from salivary proteins of the Lu. longipalpis sand fly vector. The vectors express salivary Lu. longipalpis polypeptides or variants or fragments thereof, useful in vaccine compositions for preventing or treating Leishmania infections.
Leishmaniasis is a severe parasitic disease affecting humans, canines, and felines, caused by various Leishmania species transmitted primarily by sand flies of the genus Phlebotomus and Lutzomyia, with Lu. longipalpis as the main vector in the New World. Current treatments for leishmaniasis in dogs are limited, often ineffective, and have adverse side effects. Control measures such as culling or insecticide collars are considered unacceptable, expensive, or ineffective, and no vaccine is currently available for leishmaniasis, highlighting a need for effective vaccination strategies.
The invention addresses this need by providing recombinant vectors and vaccine compositions that express Lu. longipalpis salivary antigens, along with methods for vaccination against Leishmania. These vaccines may prevent diffusion and/or replication of the parasite in the host and induce immunological or protective responses. The invention includes vectors for in vivo and in vitro expression, vaccine compositions with suitable carriers or adjuvants, methods for administering these vaccines, and kits for use in such methods, thereby offering a comprehensive approach to control leishmaniasis through immunization.
Claims Coverage
The claims of the patent focus on a vaccine composition utilizing a specific ALVAC vector and methods of vaccination, disclosing polynucleotides and vectors with specific sequences related to Lu. longipalpis salivary antigens.
Vaccine composition comprising a specific ALVAC vector
A vaccine composition containing an ALVAC vector vCP2389 that includes a polynucleotide with the sequence set forth in SEQ ID NO:94, designed for immunization against Leishmania.
Method of vaccinating a susceptible subject
A method involving at least one administration of the vaccine composition containing the ALVAC vector vCP2389 to a subject susceptible to Leishmania infection.
Subject applicability of vaccination method
The vaccination method applies to subjects selected from humans, canines, or felines, encompassing a broad range of potential hosts.
Isolated polynucleotides with specific sequence identity
Isolated polynucleotides comprising nucleotide sequences having at least 80%, 90%, or 95% sequence identity to the sequence of SEQ ID NO:22, as well as the exact sequence, encoding Lu. longipalpis salivary antigens.
ALVAC vectors comprising specific polynucleotides
ALVAC vectors incorporating polynucleotides as defined above, allowing for in vivo expression of relevant immunogens.
Host cells transformed with ALVAC vectors
Host cells genetically transformed with the described ALVAC vectors containing polynucleotides encoding Lu. longipalpis salivary polypeptides, enabling production of vaccine components in vitro.
The claims predominantly cover vaccine compositions comprising specific ALVAC viral vectors encoding Lu. longipalpis salivary antigens, methods for vaccinating susceptible hosts including humans and animals, and molecular components such as isolated polynucleotides and transformed host cells necessary for producing these vaccines.
Stated Advantages
The vaccine induces specific and significant humoral immunity with sustained antibody titers.
Vaccination elicits interferon-gamma secretion from peripheral blood mononuclear cells, indicative of a protective cellular immune response.
Vaccinated dogs exhibit immune cellular infiltration at sand fly bite sites, demonstrating induction of delayed type hypersensitivity responses.
Lymphocytes from vaccinated dogs effectively kill Leishmania chagasi amastigotes in vitro, comparable to non-specific mitogen stimulation.
Documented Applications
Vaccination of humans, canines, and felines against Leishmania infection using vaccines comprising Lu. longipalpis salivary antigens.
Use of recombinant ALVAC viral vectors expressing sand fly salivary proteins as vaccines for prevention or treatment of Leishmania infections.
Diagnostic applications for detecting infection with Leishmania by identifying antibodies specific to Lu. longipalpis salivary proteins in body fluids.
Prime-boost vaccination regimens utilizing plasmid and viral vector vaccines encoding Lu. longipalpis salivary antigens to confer protective immunity.
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