Development of DNA vaccines

Introduction

One approach generating great interest is that of inducing protective immune responses by injecting engineered DNA sequences from infectious organisms against which protection is desired. If an antigen can be identified it is possible to insert the DNA sequence coding for the protein antigen into a carrier genome (such as several of the poxviruses or alpha viruses). Once delivered into the host, the organism (and hence the inserted DNA) undergoes limited replication, the protein of interest is produced, and the host develops an immune response against the protein.

In a related strategy, so called naked DNA is injected directly into the host to produce an immune response. Naked DNA is simply sequences of DNA inserted into bacterial plasmids (simple, extrachromosomal rings of DNA found in bacterial cells) and injected into the host. These have been effective in animal models, but intramuscularly injected DNA in humans has failed to generate vigorous immune responses, although transdermal or intradermal delivery of DNA has been more encouraging. A clinical trial of transdermally delivered microscopic gold beads coated with DNA coding for hepatitis B surface antigen generated protective levels of antibodies to the antigen. This vaccine has also generated CD8 cytotoxic lymphocytes Although efforts have been successful in animal models of vaccines against several pathogens, progress in humans has been much slower. To date, only DNA vaccines against hepatitis B and malaria⁷ have induced immune responses thought to be protective in humans.

Applications

No DNA vaccines have been approved for human use in the United States. Few experimental trials have evoked a response strong enough to protect against disease and the technique's usefulness remains to be proven in humans. A veterinary DNA vaccine to protect horses from West Nile virus has been approved.

Advantages

5. No risk for infection
5. Antigen presentation by both MHC class I and class II molecules
5. Polarise T-cell response toward type 1 or type 2
5. Immune response focused on antigen of interest
5. Ease of development and production
5. Stability for storage and shipping
5. Cost-effectiveness

Adverse effects

5. Limited to protein immunogens
5. Risk of affecting genes controlling cell growth [citation needed]
5. Possibility of inducing antibody production against DNA
5. Possibility of tolerance to the antigen (protein) produced
5. Potential for atypical processing of bacterial and parasite proteins.

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