The invention is directed to a suppository based vaccine delivery system for immunizing against urogenital and anorectally transmitted infectious disease in humans and animals and a method for treating the same. More particularly, this invention is directed to a suppository based vaccine delivery system for the prophylaxis against or treatment of urogenital or anorectal transmitted infectious diseases, such as from viral or microbial pathogens. The suppository based delivery system comprises vaccine and/or vaccine adjuvant(s) comprised of whole or fractionated viral or other microbial pathogens, or their purified cellular constituents, whether native, mutated, synthetic, cloned or recombinantly expressed, that consists of nucleic acids, proteins, lipids or other antigenic determinants capable of producing humoral or cellular-mediated immunity in humans or animals; and a polyethylene glycol base; wherein the suppository is adapted to be inserted into a bodily orifice of a human or animal so as to allow the suppository to be in contact with tissue of the bodily orifice to facilitate transfer of vaccine or vaccine adjuvant(s) material therethrough.

SUMMARY OF THE INVENTION

According to the present invention, there is provided an intravaginally or intrarectally administered suppository based vaccine delivery system for prophylaxis against urogenital or anorectal localized or transmitted infectious diseases.

Further according to the present invention, there is provided a suppository based vaccine delivery system for the prophylaxis against or treatment of urogenitally or rectally transmitted or localized infectious diseases, such as bacterial, protozoal, fungal or viral infections wherein the vaccine or vaccine adjuvant is in contact with the vaginal or anorectal mucous membrane for a sufficient period of time to enhance the immune response.

Still further according to the present invention, there is provided a suppository based vaccine delivery system for the prophylaxis against or treatment of urogenitally or rectally transmitted or localized infectious diseases, such as bacterial, protozoal, fungal or viral infections, wherein the vaccine or vaccine adjuvant is easily administered, does not require the patient to lie in a supine position for an extended period of time after receiving the vaccination, and is suitably administered by the patient for primary and routine booster requirements.

Still further according to the present invention, there is provided a suppository based vaccine delivery system for prophylaxis against urogenitally or rectally transmitted or localized infectious diseases, such as bacterial, protozoal, fungal or viral infections in humans or animals, said suppository comprising: a vaccine or vaccine adjuvant containing whole or fractionated viral or other microbial pathogens, or their purified cellular constituents, whether native, synthetic, cloned or recombinantly expressed, that consists of nucleic acids, proteins, lipids or other antigenic determinants capable of producing humoral- or cellular-mediated immunity in humans or animals, wherein the suppository is comprised of a suitable base that liquefies or becomes water miscible at body temperature in order to deliver vaccine components to the urogenital or anorectal mucosa; wherein the suppository is adapted to be inserted vaginally or rectally so as to allow the suppository to be in contact with mucous membrane to facilitate transfer of vaccine or vaccine adjuvant material therethrough.

An advantage of the present invention is the provision of a suppository based vaccine delivery system for the prophylaxis against or treatment of urogenital and/or rectally transmitted or localized infectious diseases, such as viral or other pathogenic microbial infections, wherein the vaccine or vaccine adjuvant is in contact with the vaginal or rectal mucous membrane for a sufficient period of time to enhance the immune response.

Another advantage of the present invention is the provision of a suppository based vaccine delivery system wherein humoral- and/or cell-mediated stimulation from mucosal vaccination allows immune responses to specifically keep viral or microbial shedding or colonization from occurring or recurring, or prohibiting pathogen-host attachment instead of fighting the infection after it has colonized or has propagated.

Another advantage of the present invention is the provision of a suppository based vaccine delivery system wherein the suppository can be easily manufactured to allow incorporation of vaccine or vaccine adjuvant(s) with preservatives, such as thimersal; is a solid at or below room temperature for structure and to allow ease of insertion; and becomes liquified or water-miscible at body temperature so as to allow its components to enhance an immune response.

Another advantage of the present invention is the provision of a suppository based vaccine delivery system for the prophylaxis against urogenitally or rectally transmitted or localized infectious diseases, such as viral or other pathogenic microorganism infections, wherein the vaccine is easily administered, and does not require the patient to be in a supine position for an extended period of time after receiving the vaccination.

Another advantage of the present invention is the provision of a suppository based vaccine delivery system wherein the vaccine can be readily self-administered by the patient.

Another advantage of the present invention is the provision of a suppository based vaccine delivery system wherein the administration of the vaccine is relatively painless.

Yet another advantage of the present invention is the provision of a suppository based vaccine delivery system wherein the patient may self-administer booster vaccinations periodically. Still other advantages of the invention will become apparent to those skilled in the art upon a reading and understanding of the following detailed description, and appended claims.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

This invention is directed to a suppository based vaccine delivery system for immunizing against infectious disease in humans and animals and a method for treating the same. More particularly, this invention is directed to a suppository based vaccine delivery system for the prophylaxis against or treatment of urogenitally and anorectally localized or transmitted infectious diseases, such as from viral or other pathogenic microbial infections including but not limited to bacteria, protozoans, fungi and the like. The suppository based vaccine delivery system comprises a vaccine and/or vaccine adjuvant(s) comprising pathogenic microbial or viral antigenic constituents and optionally a preservative and optionally a buffer; wherein the suppository is adapted to be inserted into a bodily orifice of a human or animal so as to allow the vaccine and/or vaccine adjuvant to come in contact with the mucosal tissue of the bodily orifice to facilitate transfer of the suppository material therethrough.

The suppository comprises a vaccine and/or vaccine adjuvant(s) comprising fractionated or whole cell or purified cellular constituents whether native, mutated, synthetic, cloned or recombinantly-expressed pathogenic microbial or viral protein lipids or nucleic acid constituents that are capable of stimulating humoral- or cellular-mediated immune responses against which the pathogens or constituents correspond.

The suppository comprises a vaccine and/or vaccine adjuvant(s) that is prepared by either purifying native pathogen constituents, by synthesis or recombinant expression of protein or genetic components of native pathogens or by purifying synthetic, mutated or cloned pathogen-derived nucleic acid sequences.

The suppository of the present invention comprises any suitable suppository base known in the art. More particularly, the suppository base comprises material that is solid or semi-solid at or below room temperature but liquefies or becomes water-miscible at body temperature. The suppository base includes but is not limited to polyethylene glycol, triglycerides, fatty acids, fatty alcohols, glycerin and the like. Preferably the suppository base is polyethylene glycol. The suppository base optionally includes emulsifying agents such as polysorbate, gelatin, methylcellulose, alginic acid, sodium lauryl sulfate, and the like.

The suppository base is present in the delivery system in any suitable amount so as to allow the incorporation of the vaccine or vaccine adjuvant(s) in a solid or semi-solid form so that the structural integrity is maintained or that insertion into a body orifice can be easily performed. When inserted, the suppository base liquefies or becomes water-miscible at body temperature so as to allow the vaccine and/or vaccine adjuvant components to become in contact with the mucous membrane for a sufficient period of time to enhance the immune response. The weight percent of the suppository base is dependent upon the size of the bodily orifice of the human and/or the animal, the dosage of vaccine and/or vaccine adjuvant(s) necessary to elicit an immune response and its physiochemical characteristics that allow it to remain solid at or below room temperature. The suppository comprises from about 50% to greater than 99%, preferably about 75% to greater than 99% by weight of the suppository base. Preferably the suppository comprises about 75% to about 98% by weight polyethylene glycol. Preferably the suppository comprises about 2% to about 25% by weight polysorbate. The suppository base has a molecular weight in the range of about 400 to about 5000, preferably about 950 to about 3700. In a more preferred embodiment, the polyethylene glycol suppository base is comprised of about 39% by weight of polyethylene glycol having a molecular weight of about (3000) and about 59% by weight of polyethylene glycol having a molecular weight of about 400. A suitable commercially available polyethylene glycol suppository base is POLYBASE, available from Paddock Laboratories, Inc.

The suppository base optionally includes either or both of a preservative(s) and a buffer(s). The preservative is selected from the group consisting of thimersal, benzoic acid, benzoic acid derivatives, benzylkonium, benzylkonium chloride sulfites, quaternary ammonium salts, chlorobutanol and combinations thereof at concentrations ranging from about 0.01% to about 0.5%. The buffers are employed so that the pH of the suppository vaccine remains the same. The buffers used are those known in the art and include, but are not limited to citrate, phosphate, hepes (or their salts) and combinations thereof at a concentration in the range of about 5 milimolar to about 0.5 molar.

The suppository base confers a degree of miscibleness with the mucous membrane surfaces of the vagina or rectum, wherein suspended particles of the vaccine and/or vaccine adjuvant(s) are in contact with such mucous membrane surfaces for a sufficient amount of time to elicit a humoral- or cell-mediated immune response. The suppository base has an adjuvant effect that enhances the immune response by allowing the vaccine to facilitate contact time with the vaginal or anorectal tract mucous membranes, serving as a depot that slowly releases antigen, and by localizing and delivering antigens to immunocompetent cells. The suppository base possesses properties that allow the suppository to be molded in a desirable form and further function as a structural necessity that keeps the suppository in its desired molded form at or below room temperature.

The suppository is allowed to harden in a suppository shell or a mold that forms the desired shape. The suppository is generally stored in the shell until used or is removed from the mold and repackaged. The suppository shell or mold is any shell or mold known in the art suitable for molding or packaging of the suppository. A suitable commercially available laminate suppository shell is a polyvinylchloride polyethylene laminate suppository shell available from Paddock Laboratories, Inc.

The suppository based vaccine delivery system of the present invention is prepared by general techniques known in the art. Typically, the suppository base vaccine delivery system is prepared under a sterile environment. The suppository base is heated in a sterile environment to a temperature in the range of its melting point to liquefy the base. The suppository base is heated for a time sufficient to liquefy it without degrading it.

The vaccine or vaccine adjuvant(s) comprising the whole or fractionated viral or other microbial pathogen, or their purified cellular constituents or derivatives, whether native, mutated, synthetic, cloned or recombinantly expressed, that consist of nucleic acids, proteins, lipids or other antigenic determinants capable of producing humoral- or cullular-mediated immunity is placed in a container containing the liquified suppository base. The vaccine and/or vaccine adjuvant(s) are stirred with the liquid suppository base until a homogeneous suspension is produced. A preservative or adjuvant is added and stirred until a homogeneous suspension is again attained. The suspension comprising the suppository base and the vaccine and/or vaccine adjuvant(s) and preservative is placed into individual laminate suppository shells. The suppository is then cooled at room temperature to allow it to harden. The suppositories are then heat-sealed and stored at refrigerated temperature.

The suppository based vaccine delivery system according to the present invention when inserted into a bodily orifice and allowed to liquify or become water-miscible allows the vaccine to be in contact with the vaginal or rectal tract mucous membrane for a sufficient period of time to enhance the immune response. Further, the suppository based vaccine delivery system according to the present invention allows the incorporation of vaccine, vaccine adjuvant(s) and preservative and is easily administered, does not require the patient to lie in a supine position for an extended period of time after receiving the vaccination, is suitably administered by the patient, is painless, is amenable to routine booster vaccinations and allows a favorable method of antigen delivery to immunocompetent cells through the mucosa.
 

Claim 1 of 4 Claims

1. A method for producing an immune response in humans, said method comprising the steps of: (a) contacting a suppository with mucosal tissue of a human at and internal to the urogenital orifice, wherein said suppository comprises an immunogen or vaccine adjuvant(s) of microbial pathogens, capable of producing humoral or cellular-mediated immunity against urogenital disease in humans and a suppository base, wherein the suppository base comprises about 98% of polyethylene glycol and about 2% of polysorbate, to facilitate transfer of the immunogen or vaccine adjuvant material therethrough and induce an immune response in the human.
 

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