Leishmania vaccine using sand fly salivary immunogen
Inventors
Fischer, Laurent • Kamhawi, Shaden • Valenzuela, Jesus • Ribeiro, Jose
Assignees
Boehringer Ingelheim Animal Health USA Inc • US Department of Health and Human Services
Publication Number
US-9228002-B2
Publication Date
2016-01-05
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 in vivo or in vitro sand fly Lutzomyia longipalpis salivary antigens that elicit an immune response in animals or humans against Leishmania. These include recombinant vectors such as recombinant viruses, particularly recombinant poxviruses, carrying and expressing exogenous nucleic acid molecules encoding immunogens or epitopes derived from Lu. longipalpis salivary proteins, or variants or fragments thereof. Vaccine compositions comprising these vectors and/or the salivary polypeptides themselves, as well as methods of vaccination against Leishmania and diagnostic kits, are also provided.
Leishmaniasis is a major and severe parasitic disease affecting humans, canines, and to a lesser degree felines, caused by various Leishmania species and transmitted primarily by sand flies of the genera Phlebotomus and Lutzomyia. The disease presents clinically in various forms, with cutaneous and visceral manifestations, and dogs are considered major reservoirs. Current treatment options for leishmaniasis in dogs have limited effectiveness, with issues including drug resistance and side effects. Control measures such as culling seropositive dogs or insecticide use have limitations, and mathematical models suggest that developing a vaccine for canines is the most practical and effective method to control the disease.
Claims Coverage
The patent disclosure includes multiple independent claims focused on compositions and vectors involving LJM17 polypeptides and their encoding polynucleotides, particularly in vaccine constructs against Leishmania.
Composition comprising expression vectors encoding LJM17 polypeptides
A composition comprising an expression vector selected from pVR2001-TOPO, pVR2001-TOPA and ALVAC, containing a polynucleotide encoding one or more LJM17 polypeptides with at least 80% sequence identity to polypeptides SEQ ID NO: 5, 7, 15, or 17.
Inclusion of Leishmania antigens in compositions
The composition can further comprise at least one Leishmania antigen, such as KMP11 or inactivated Leishmania, to enhance vaccine efficacy.
Vectors comprising polynucleotides encoding LJM17 polypeptides
Vectors include one or more polynucleotides encoding LJM17 polypeptides having at least 80% sequence identity to specified sequences and utilize in vivo or in vitro expression vectors including pVR2001-TOPO, pVR2001-TOPA, and ALVAC.
Method of vaccinating a subject susceptible to Leishmania
A method of vaccinating humans, canines, or felines against Leishmania using the described compositions or vectors encoding LJM17 polypeptides to induce protective immunity.
The claims cover compositions and vectors encoding specific Lu. longipalpis salivary polypeptides (notably LJM17), optionally combined with Leishmania antigens, and methods of vaccination using these constructs to protect susceptible hosts from Leishmania infection.
Stated Advantages
The vaccines may prevent diffusion and/or replication of the Leishmania parasite in a host.
Vectors and vaccine formulations fulfill the long-felt need for an effective vaccine against Leishmania.
Vaccination induces specific humoral and cell-based immune responses, including IFN-gamma secretion, that are associated with protective immunity.
Documented Applications
Vaccination of animals and humans against Leishmania infection to prevent disease progression and parasite dissemination.
Use of recombinant vectors expressing Lu. longipalpis salivary antigens as vaccines or immunological compositions.
Use of Lu. longipalpis salivary polypeptides, antibodies thereto, and vectors encoding them in diagnostic assays for detection of Leishmania infection.
Prime-boost vaccination regimens involving plasmid-based vaccines, recombinant viral vector vaccines, and sub-unit vaccines to enhance protective immune responses in hosts.
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