Vaccine and methods of use against Strongyloide stercoralis infection
Inventors
Nutman, Thomas B. • Abraham, David
Assignees
Thomas Jefferson University • US Department of Health and Human Services
Publication Number
US-9056068-B2
Publication Date
2015-06-16
Expiration Date
2031-02-01
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Abstract
The polynucleotide encoding the SSIR gene from the nematode Strongyloides stercoralis is provided, along with the polypeptide encoded by the SSIR gene. It was found that when mice were immunized with the SSIR polypeptide vaccine, it provided immunity to mice which were implanted with Strongyloides stercoralis L3 implants. Methods for making the SSIR protein, recombinant vectors encoding the SSIR gene, a vaccine made from the SSIR protein, and methods of use are also provided.
Core Innovation
The invention provides a polynucleotide encoding the Strongyloides stercoralis immunoreactive antigen (SSIR) gene and the polypeptide encoded by the SSIR gene. It has been discovered that immunization of mice with the SSIR polypeptide vaccine provides immunity against Strongyloides stercoralis infection. Specifically, mice immunized with the SSIR antigen showed 70-90% protection from challenge infection with S. stercoralis larvae. Additionally, sera from these immunized mice, when transferred to naive mice, conferred protection against infection to the naive mice.
The invention includes methods for producing the SSIR protein through recombinant expression in various systems, compositions comprising the SSIR polypeptide or corresponding polynucleotide with pharmaceutically acceptable carriers and adjuvants, and methods of vaccinating mammals against S. stercoralis infection by administering these compositions under conditions sufficient to induce protective immune responses. It further provides for the use of the SSIR antigen to identify analogous antigens in other parasitic nematodes and for use as an immunosuppressant in allergies.
The problem being addressed arises from the nematode Strongyloides stercoralis which infects millions globally and causes chronic infections that can be subclinical but pose a life-threatening risk when the host becomes immunosuppressed, leading to hyperinfection syndrome. Current treatments for hyperinfection are problematic, necessitating the development of new immunostimulatory compositions and vaccines. There was a lack of effective vaccine candidates for this infection prior to the discovery of the SSIR antigen.
Claims Coverage
The patent contains two independent claims focusing on pharmaceutical compositions and methods for inducing immune responses using the SSIR antigen.
Pharmaceutical composition comprising SSIR antigen with adjuvant and carrier
A pharmaceutical composition containing an isolated antigen from Strongyloides stercoralis stage L3 comprising the SSIR protein (SEQ ID NO: 2 or encoded by SEQ ID NO: 1), combined with an adjuvant such as alum, and a pharmaceutically acceptable carrier.
Vaccine effective for protecting mammals against Strongyloides stercoralis infection
A vaccine formulation comprising an effective amount of the isolated SSIR antigen from Strongyloides stercoralis stage L3, an adjuvant (e.g., alum), and a pharmaceutically acceptable carrier, which protects mammals against Strongyloides stercoralis infection.
Method of inducing protective immune response in mammals
A method of administering the pharmaceutical composition including the SSIR antigen and adjuvant to a mammal in an effective dose (0.001 to 1000 mg/kg body weight per day) to induce an immune response that kills Strongyloides stercoralis larvae and confers protection against infection. Administration routes include intranasal, intradermal, subcutaneous, intramuscular, or intravenous.
The claims collectively cover pharmaceutical compositions and vaccines containing the SSIR antigen with adjuvants that induce protective immunity against Strongyloides stercoralis in mammals, as well as the methods of immunization that provide significant protective efficacy and increase antibody titers.
Stated Advantages
Immunization with the SSIR antigen provides 70-90% protection against challenge infection with Strongyloides stercoralis larvae.
Protective immunity can be passively transferred by sera from immunized hosts to naive hosts.
The SSIR protein-based compositions elicit increased anti-Strongyloides stercoralis antibody titers in treated mammals compared to untreated mammals.
Documented Applications
A vaccine for vaccinating mammals, including humans, against infection by Strongyloides stercoralis using a composition comprising the SSIR antigen and adjuvants such as alum.
A pharmaceutical composition used as a medicament to induce an immune response and protective immunity against Strongyloides stercoralis infection in subjects.
Use of the SSIR antigen to identify analogous antigens in other parasitic nematodes for potential use in vaccines against other nematode infections such as hookworms or filarial worms.
Use of the SSIR antigen or its polynucleotide to reduce allergic activity in subjects by providing an immunosuppressant effect against severe allergies.
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