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The implications of a successful vaccine for HIV are monumentous. With recent statistics of this growing epidemic in South Africa and other underdeveloped countries, the need for scientific focus is becoming increasingly apparent. To this point large advances have been made in the form of general knowledge and treatment for HIV and AIDS. A successful vaccine (safely protect human host from live challenge), however, has yet to be accomplished. Many characteristics of HIV combine to make it very difficult to induce a strong and specific immune response to viral infection. Possibly the most dramatic of these characteristics is its high vicissitude, enabling the virus to change antigenic properties and therefore escape specific immune mechanisms of human hosts. In light of this, it seems imperative to optimize the immunogenicity of partially conserved regions of antigenic proteins within the virus. Along with this requirement for specificity, an efficacious vaccine will likely need to induce humoral response which deters extracellular pathogenic advance, as well as, cell-mediated immunity, which focuses on the destruction of pathogen-infected cells.
There are currently many different approaches to HIV vaccination at many phases of experimentation. Attenuated vaccines (weakened forms of live HIV) have been successful in eliciting adequate immunity, however the safety of such methods is very questionable. Other types of vaccination, such as protein-based immunizations, have primarily been shown to induce antibody response but not complete defense. Finally, although fairly new, DNA vaccines and DNA vaccine in combination with protein “boosting” are very promising in their ability to confer adequate protection for HIV and a variety of other viral, bacterial, and parasitical pathogens.
Using recombinant DNA technology, antigenic genes derived from pathogens are cloned into bacterial plasmids expressing mammalian expression sequences (promoters, poly A tails, etc.). The construct is then injected into the host in a number of different possible modes of entry-including intramuscular, gene-gun, and mucosal introduction. The DNA is taken up by certain antigen presenting cells (depending on route of entry) and is then expressed by host cellular machinery. Analogous to live or live attenuated viruses, the antigenic proteins are endogenously produced and therefore DNA vaccines are able to induce both CTL and antibody response (without generating the same risk of their counterpart).
Another positive characteristic of DNA vaccines is their compatibility with both chemical and genetic adjuvants. For instance, more than one antigen can be cloned within the same vector. This offers the advantage of a more accurate antigenic response and subsequent immune defense. The addition of immunomodulators such as cytokines and chemical adjuvants such as cationic liposomes have also been shown to increase the immunogencity of cloned antigens.
With current technologies, so-called codon-optimization has also proven feasible and beneficial to DNA vaccination. Codon optimization involves replacing wild type DNA sequences with more highly expressed mammalian sequences (without changing the antigen). Because studies have indicated a direct correlation with expression levels and immunogenicity - the reason to codon-optimize is clear.
Additionally, DNA vaccines are inexpensive, easy to store/transport, and are relatively simple to produce- making them excellent candidates for large-scale immunizations. Because production of DNA vaccines does not constitute culturing dangerous pathogens and it in itself contains no pathogenic repercussions, their safety has been consistent. For these reasons, DNA vaccines have been studied and developed for a plethora of pathogens including HIV.
Numerous animal tests and a few human trials have indicated the promise of DNA based immunity for HIV infection. However, preliminary results from DNA vaccinations have revealed more investigation is needed to perfect the efficacy of this method of immunization. Through methods described here, as well as others, DNA vaccination for HIV must conquer tow obstacles 1) conferring protection against a myriad of strains and 2) eliciting a more potent, complete immune response.
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