Vaccine and drug delivery by topical application of vectors and vector extracts

Abstract

Disclosed and claimed are methods of non-invasive immunization and drug delivery in an animal and/or methods of inducing a systemic immune or therapeutic response in an animal following topical application of non-replicative vectors, products therefrom and uses for the methods and products therefrom. Also disclosed and claimed are methods of non-invasive immunization and drug delivery in an animal and/or a method of inducing a systemic immune response or systemic therapeutic response to a gene product comprising contacting skin of the animal with cell-free extracts in an amount effective to induce the response, wherein the extracts are prepared by filtration of disrupted cells, wherein the cell comprises and expresses a nucleic acid molecule. Preferably, the cell is temporarily disrupted by sonication, remaining intact and viable after the sonication. Also, methods are disclosed and claimed for enhancing the immunogenicity and efficacy of an epicutaneous vaccine for inducing a systemic immune response to an antigen, in an animal comprising contacting skin of the animal with vaccines admixed with heat-shock protein 27, in an amount effective to induce the response. The methods include contacting skin of the animal with a vector in an amount effective to induce the systemic immune or therapeutic response. The vector can include and express an exogenous nucleic acid molecule encoding an epitope or gene product of interest. The systemic immune response can be to or from the epitope or gene product. The nucleic acid molecule can encode an epitope or antigen of interest and/or a nucleic acid molecule that stimulates and/or modulates an immunological response and/or stimulates and/or modulates expression, e.g., transcription and/or translation, such as transcription and/or translation of an endogenous and/or exogenous nucleic acid molecule; e.g., one or more of influenza hemagglutinin, influenza nuclear protein, influenza M2, tetanus toxin C-fragment, anthrax protective antigen, anthrax lethal factor, anthrax germination factors, rabies glycoprotein, HBV surface antigen, HIV gp120, HIV gp160, human carcinoembryonic antigen, malaria CSP, malaria SSP, malaria MSP, malaria pfg, botulinum toxin A, and mycobacterium tuberculosis HSP; and/or a therapeutic, an immunomodulatory gene, such as co- stimulatory gene and/or a cytokine gene. The immune response can be induced by the vector expressing the nucleic acid molecule in the animal's cells including epidermal cells. The immune response can also be induced by antigens expressed from the nucleic acid molecule within the vector. The immune response can be against a pathogen or a neoplasm. A prophylactic vaccine or a therapeutic vaccine or an immunological composition can include the vector. The animal can be a vertebrate, e.g., a mammal, such as human, a cow, a horse, a dog, a cat, a goat, a sheep or a pig; or fowl such as turkey, chicken or duck. The vector can be one or more of a viral vector, including viral coat, e.g., with some or all viral genes deleted therefrom, bacterial, protozoan, transposon, retrotransposon, and DNA vector, e.g., a recombinant vector; for instance, an adenovirus, such as an adenovirus defective in its E1 and/or E3 and/or E4 region(s) and/or all adenoviral genes.

Description

[0001] This application is a continuation-in-part of U.S. patent application Ser. No. 10 / 116,963, filed Apr. 5, 2002, which is a continuation-in-part of U.S. patent application Ser. No. 10 / 052,323, filed Jan. 18, 2002, which is a continuation-in-part of U.S. patent application Ser. No. 09 / 563,826, filed May 3, 2000 (issued Feb. 19, 2002 as Patent No. 6,348,450), which claims priority from U.S. Provisional Application No. 60 / 132,216, filed May 3, 1999, and is also a continuation-in-part of U.S. patent application Ser. No. 09 / 533,149, filed Mar. 23, 2000, which in turn is a continuation of U.S. patent application Ser. No. 09 / 402,527, filed on Aug. 13, 2000. Each of these applications and each of the documents cited in each of these applications ("application cited documents"), and each document referenced or cited in the application cited documents, either in the text or during the prosecution of those applications, as well as all arguments in support of patentability advanced during ...

AI Technical Summary

Benefits of technology

0041] Non-invasive vaccination onto the skin (NIVS) can improve vaccination schemes because skin is an immunocompetent tissue and this non-invasive procedure requires no specially trained personnel. Skin-targeted non-invasive gene delivery can achieve localized transgene expression in the skin and the elicitation of immune responses (Tang et

Problems solved by technology

Inoculation of vaccines in an invasive mode requires equipment and personnel with special medical training, and is usually associated with discomfort and potential hazards (bleeding, infection).

Although U.S. Pat. No. 3,837,340 relates to a method for vaccinating animals by contacting skin with dried viruses, the viruses that are employed therein are not genetic vectors capable of expressing transgenes or heterologous or exogenous nucleic acid molecules.

However, this

Images