Phlebotomus ariasi; inducing an immune response to sand fly saliva; treating or preventing Leishmaniasis
Inventors
Valenzuela, Jesus G. • Ribiero, Jose M. C. • Kamhawi, Shaden • Belkaid, Yasmine • Fischer, Laurent • Audonnet, Jean-Christophe • Milward, Francis
Assignees
HEALTH AND HUMAN SERVICES GOVERNMENT OF United States, THE, Secretary of, Department of • MERIAL Ltd • SECRETARY OF DEPARTMENT OF HEALTH AND HUMAN SERVICES GOVERNMENT OF United States, AS REPRESENTED BY • Merial LLC • US Department of Health and Human Services
Publication Number
US-7741437-B2
Publication Date
2010-06-22
Expiration Date
2023-09-18
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Abstract
Substantially purified salivary P. ariasi and P. perniciosus polypeptides, and polynucleotides encoding these polypeptides are disclosed. Vectors and host cells including the P. ariasi and P. perniciosus polynucleotides are also disclosed. In one embodiment, a method is disclosed for inducing an immune response to sand fly saliva. In other embodiments, methods for treating or preventing Leishmaniasis are disclosed.
Core Innovation
The present disclosure relates to substantially purified salivary polypeptides from Phlebotomus ariasi and Phlebotomus perniciosus sand flies, as well as polynucleotides encoding these polypeptides. It also encompasses vectors and host cells including the P. ariasi and P. perniciosus polynucleotides. The disclosure provides methods for inducing an immune response to sand fly saliva by administering therapeutically effective amounts of these polypeptides or their encoding nucleic acids. Additionally, methods for treating or preventing Leishmaniasis in subjects using these polypeptides or nucleotides are disclosed, alongside pharmaceutical compositions containing these components.
The problem addressed by this invention is the lack of an effective vaccine against Leishmaniasis, a group of diseases caused by Leishmania protozoa, transmitted through phlebotomine sand flies. Sand fly saliva contains compounds that facilitate blood feeding and modulate the host immune response. Despite knowledge about sand fly saliva's role in disease transmission, much remains unknown, and there is a need for agents capable of inducing an immune response to prevent or treat Leishmania infections.
The disclosure identifies salivary proteins specifically from the P. ariasi and P. perniciosus species, both proven vectors of visceral Leishmaniasis in the Old World. By isolating and characterizing these polypeptides and their encoding nucleic acids, the invention provides immunogenic compositions and recombinant vectors useful for vaccination. Administering these compositions induces immune responses against sand fly saliva, which can indirectly protect against or reduce symptoms of Leishmania infection by eliciting cellular immunity, such as a Th1 response.
Claims Coverage
The patent includes 10 claims featuring one independent claim focusing on purified P. ariasi polypeptides and related immunogenic compositions.
Substantially purified P. ariasi salivary polypeptide
A substantially purified salivary Phlebotomus ariasi polypeptide comprising residues 23-312 of SEQ ID NO: 11, or at least 95% identical sequences, or immunogenic fragments thereof containing at least fifteen contiguous amino acids.
Immunogenic compositions comprising P. ariasi polypeptides
Compositions including an effective amount of the substantially purified P. ariasi polypeptide (residues 23-312 of SEQ ID NO: 11 or its variants) and a pharmaceutically acceptable carrier.
The claims cover substantially purified P. ariasi salivary polypeptides within specified sequence identity ranges or immunogenic fragments thereof, and immunogenic compositions comprising these polypeptides combined with pharmaceutically acceptable carriers.
Stated Advantages
The immunogenic compositions elicit an immune response to sand fly salivary proteins, leading to reduced symptoms and parasite load of Leishmania infection.
Inducing a Th1 type immune response to sand fly saliva can indirectly kill Leishmania parasites by enhancing macrophage activation and antigen presentation.
Documented Applications
Inducing an immune response to sand fly saliva in subjects to prevent or treat Leishmaniasis.
Use in immunogenic compositions or vaccines comprising P. ariasi and/or P. perniciosus salivary polypeptides or their encoding nucleic acids.
Administration of vaccines to human or veterinary subjects, including dogs, to confer resistance to Leishmania infection.
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