Biomarkers and immunogenic compositions for filarial parasites
Inventors
Lustigman, Sara • Nutman, Thomas B. • BENNURU, Sasisekhar
Assignees
United States Department Of Health And Human Services Office Of Technology Transfer • New York Blood Center Inc • US Department of Health and Human Services
Publication Number
US-12251432-B2
Publication Date
2025-03-18
Expiration Date
2037-03-31
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
Disclosed herein are immunogenic compositions for preventing or treating infection with filarial parasites and biomarkers for diagnosing infection with filarial parasites.
Core Innovation
The invention relates to immunogenic compositions for preventing or treating infection with filarial parasites, specifically Onchocerca volvulus and Dirofilaria immitis, as well as biomarkers for diagnosing these infections. The immunogenic compositions comprise selected filarial parasite proteins or their orthologs sharing high sequence identity to defined sequences (SEQ ID NOs), which can be provided as mixtures or fusion proteins, optionally with adjuvants. Methods for preventing infection or transmission through administration of such immunogenic compositions are disclosed, along with methods to detect infection by identifying specific filarial proteins or antibodies thereto in biological samples.
The problem addressed arises from the limitations of current onchocerciasis control relying principally on ivermectin-based mass drug administration (MDA). The challenges include the possibility that elimination cannot be achieved solely through MDA, risks associated with co-endemic infections like Loa loa, and the emergence of ivermectin resistance in canine heartworm control. There is a need for additional tools such as macrofilaricidal drugs, vaccines, and sensitive diagnostic biomarkers, which depend on a thorough understanding of the parasite biology and parasite-host interactions.
The invention solves these problems by providing a comprehensive characterization of the stage-specific transcriptomes and proteomes of O. volvulus, enabling identification of novel vaccine candidates and diagnostic biomarkers. The disclosed immunogenic compositions utilize filarial parasite proteins that elicit protective immune responses, including proteins with stage-specific expression profiles. The invention also facilitates the use of orthologous proteins from D. immitis to protect dogs against heartworm infection, addressing emerging drug resistance issues. The diagnostic methods enable sensitive detection of infection by identifying specific proteins or antibodies associated with filarial parasites in patient samples.
Claims Coverage
The patent claims encompass three independent immunogenic compositions for administration to canine subjects, each involving distinct combinations of isolated Dirofilaria immitis proteins and adjuvants. The claims cover compositions comprising specific proteins alone or in combination, their presentation as mixtures or fusion proteins, and compositions inducing immune responses in canines.
Immunogenic composition with two D. immitis proteins and adjuvant
An immunogenic composition comprising isolated Dirofilaria immitis proteins including a first protein having at least 95% sequence identity to SEQ ID NO:48 and a second protein having at least 95% sequence identity to full length mature SEQ ID NO:49, combined with an adjuvant. The two proteins can be presented as a mixture or as a fusion protein optionally including linker sequences.
Immunogenic composition with three or four D. immitis proteins and adjuvant
An immunogenic composition comprising isolated Dirofilaria immitis proteins including the two proteins of the previous feature plus a third, and optionally a fourth, protein each having at least 95% sequence identity to full length mature D. immitis proteins of SEQ ID NOs:33-47, combined with an adjuvant. The third and fourth proteins are distinct from each other.
Immunogenic composition with three distinct D. immitis proteins and adjuvant inducing immune response
An immunogenic composition comprising isolated Dirofilaria immitis proteins consisting of three proteins: (i) a first protein having at least 95% sequence identity to SEQ ID NO:48; (ii) a second protein having at least 95% sequence identity to one of SEQ ID NOs:33-47 or 49; (iii) a third protein having at least 95% sequence identity to one of SEQ ID NOs:33-47 or 49, with the second and third proteins being different, combined with an adjuvant, wherein the composition induces an immune response against the D. immitis proteins in a canine subject.
The claims cover immunogenic compositions for canine administration that include specific isolated D. immitis proteins with defined sequence identity thresholds, presented singularly, as mixtures or fusion proteins, with or without inclusion of additional proteins, all formulated with an adjuvant to induce protective immune responses.
Stated Advantages
Provides immunogenic compositions including protective filarial parasite proteins capable of preventing or treating infection with filarial parasites such as O. volvulus and D. immitis.
Offers sensitive diagnostic biomarkers enabling detection of active filarial parasite infections through identification of parasite proteins or specific host antibodies.
Allows for induction of protective immunity in humans and canines, addressing the limitations of current ivermectin-based treatments, including drug resistance and adverse effects.
Facilitates development of vaccines comprising multiple filarial proteins, either as mixtures or fusion proteins, enhancing immunogenicity and potential protective efficacy.
Documented Applications
Preventing or treating infection with Onchocerca volvulus in humans through administration of immunogenic compositions comprising specific filarial parasite proteins.
Preventing transmission of O. volvulus by immunizing subjects at risk to interrupt the infection cycle.
Preventing infection with Dirofilaria immitis in canine subjects by administering immunogenic compositions comprising specified D. immitis proteins or orthologs thereof.
Diagnosing infection with O. volvulus by detecting specific filarial proteins or antibodies in specimens such as blood, skin biopsy, or urine using methods including ELISA, dipstick tests, lateral flow, microfluidic devices, luciferase immunoprecipitation systems, luminex, multiplex formats, polymerase chain reaction, and microarrays.
Interested in licensing this patent?