Immunogenic compositions and vaccines for preventing or treating filarial disease
Inventors
Mitre, Edward E. • Morris, Christopher • BENNURU, Sasisekhar • NUTMAN, Thomas
Assignees
Henry M Jackson Foundation for Advancedment of Military Medicine Inc • US Department of Health and Human Services
Publication Number
US-10441642-B2
Publication Date
2019-10-15
Expiration Date
2036-03-17
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Abstract
The present disclosure is directed to an immunogenic composition including: at least one or at least two isolated polypeptides or immunogenic fragments thereof, and optionally a pharmaceutically acceptable carrier, wherein each polypeptide is expressed on a luminal surface of an intestine of a filarial worm, wherein each polypeptide is expressed at a level at least two-fold higher in the intestine in comparison to the level of expression of each polypeptide in a reproductive tract or a body wall of the filarial worm, wherein each isolated polypeptide has at least one transmembrane domain, and wherein each polypeptide is a non-mitochondrial polypeptide. Also provided herein is a method for preventing or treating a filarial disease.
Core Innovation
The invention provides an immunogenic composition comprising at least one or at least two isolated polypeptides or immunogenic fragments thereof, optionally with a pharmaceutically acceptable carrier, where each polypeptide is expressed on the luminal surface of the intestine of a filarial worm. Each polypeptide is expressed at a level at least two-fold higher in the intestine compared to the reproductive tract or body wall of the worm, has at least one transmembrane domain, and is a non-mitochondrial polypeptide. The disclosure also includes methods for preventing or treating filarial diseases by administering such compositions.
The problem addressed is the challenge in designing effective vaccines against filarial worms, which cause major diseases like lymphatic filariasis. Individuals previously exposed to worm antigens often have IgE antibodies leading to allergic reactions upon re-exposure. Intestinal antigens may be hidden during natural infection, making them promising targets for vaccines, but previous use of intestinal homogenates gave variable efficacy. Additionally, there is a need for improved immunogenic compositions to prevent or treat diseases caused by filarial worms such as lymphatic filariasis, river blindness, loiasis, and heartworm.
Claims Coverage
The patent contains a set of independent claims focusing on an immunogenic composition and methods to treat filarial diseases using compositions comprising specific polypeptides and adjuvants.
Immunogenic composition comprising isolated polypeptides and an adjuvant
An immunogenic composition that includes at least two isolated polypeptides or immunogenic fragments thereof, specifically comprising a first polypeptide having the amino acid sequence of SEQ ID NO: 1 and a second polypeptide having the amino acid sequence of SEQ ID NO: 9, together with an adjuvant. The immunogenic fragments comprise at least 30 contiguous amino acids from the sequences of SEQ ID NO: 1 and SEQ ID NO: 9.
Inclusion of additional polypeptides in the immunogenic composition
The immunogenic composition may further contain one or more polypeptides having amino acid sequences selected from SEQ ID NOS: 2-7, 11, 14, 15, 18, 19, 22, 23, and 26.
Composition consisting essentially of five isolated polypeptides and an adjuvant
The immunogenic composition can consist essentially of five isolated polypeptides and the adjuvant.
Use of the immunogenic composition as a vaccine
The immunogenic composition is claimed as a vaccine.
Use of Freund's complete adjuvant as the adjuvant
The adjuvant in the immunogenic composition can be Freund's complete adjuvant.
Method of treating filarial disease by administering vaccine
A method for treating filarial disease by administering an effective amount of a vaccine comprising the immunogenic composition described.
Method applicability for various filarial diseases
The method applies to filarial diseases including lymphatic filariasis, river blindness, loiasis, and heartworm.
Method administration to human subjects
The method can be performed where the subject treated is a human.
Method administration for heartworm disease
The method specifically covers treatment of heartworm disease.
Method administration to canine subjects
The subject for treatment can be a dog.
Various administration routes for the vaccine
The vaccine can be administered subcutaneously, intradermally, orally, or nasally.
The claims collectively cover an immunogenic composition containing specific isolated polypeptides derived from filarial worms with an adjuvant, methods of treating filarial diseases using these compositions, and various details regarding the composition makeup, specific polypeptides, adjuvant choice, target diseases, subjects, and administration routes.
Stated Advantages
The compositions using intestinal luminal surface polypeptides have a lower potential for eliciting allergic reactions in previously infected individuals due to the hidden nature of intestinal antigens during natural infection.
Using defined isolated polypeptides from the filarial intestine in vaccines may be more effective than crude homogenates by ensuring sufficient amounts of effective antigen are present.
The identified intestinal polypeptides are conserved across major filarial pathogens, suggesting potential as pan-filarial vaccine candidates effective against multiple filarial diseases including lymphatic filariasis, river blindness, loiasis, and heartworm.
Documented Applications
Preventing or treating diseases caused by filarial worms including lymphatic filariasis, river blindness, loiasis, and heartworm disease using immunogenic compositions or vaccines comprising isolated intestinal polypeptides of filarial worms.
Administration of these immunogenic compositions or vaccines to subjects at risk of or suffering from filarial diseases, including humans and non-human animals such as dogs (particularly for heartworm).
Use of these compositions in veterinary applications, especially for canine heartworm disease prevention or treatment.
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