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192   Development of an Inactivated HIV Vaccine  

P. O. Ilyinskii*, L. Lallos, and T. Castor
Aphios Corp., Woburn, MA, USA


In the last few years, significant breakthroughs have been made in the field of AIDS treatment and anti-HIV therapy. Mixtures of drugs directed at viral protease and reverse transcriptase have proven to be effective in lowering the viral load and slowing the progression of AIDS. These new cocktail therapies are, however, quite expensive with an estimated annual cost of $12,000. Therefore, only a small amount of HIV-infected individuals can afford these treatments. There are also questions about the long-term efficacy of these therapies and other matters arising from the need to maintain a daily drug regimen.
Thus, there is thus an urgent need to develop and test alternative, less expensive interdictions for AIDS, namely a safe and effective vaccine against HIV. The whole inactivated HIV preparation may prove to be an important component of a successful vaccination regimen. Historically, killed HIV vaccines did not exhibit strong immunogenicity and protective efficacy. The underlying reason for it was a total or near-total disruption of virion structure during thermal or chemical inactivation and, as a consequence, the immune response was directed against those viral epitopes that are irrelevant to the protection from HIV infection. These concerns are addressed by novel virus inactivation technology, SuperFluids CFI. This technique utilizes gases that, when compressed, exhibit enhanced solvation, penetration, and explosive decompression properties. These gases are utilized to penetrate and inflate the viral particles. The overfilled particles are then decompressed and, as a result of rapid phase conversion, rupture at their weakest points. The aim is to introduce minimal controlled damage to the structure of the virion, rendering it noninfective, but at the same time preserving its overall tertiary structure and possibly even exposing some internal epitopes, which are usually inaccessible to the immune system. The technique is purely physical and does not rely on denaturing heat, chemicals, or irradiation.
Most of the gases used in our experiment were very efficient, inactivating more than 5 logs of HIV TCID50. Furthermore, SuperFluids CFI has minimal impact on protein integrity and antigenicity. This technique would also allow for the creation of HIV vaccines from nef-deleted and other attenuated HIV strains for a greater degree of product safety and from combinations of different HIV strains for broader protection. This HIV vaccine manufacturing technology is inexpensive, amenable to large-scale processing, and quite portable; i.e., it can be readily implemented in a host country site.


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