Chemokine microbicides

At a presentation on World AIDS day last week, anti-HIV microbicides were discussed. One microbicide, PSC-RANTES, showed considerable effectiveness but was proclaimed to be too costly and unsuitable for common use especially in developing countries. This paper therefore caught my attention as it talks about analogues to that microbicide that do have suitable characteristics for common use. The analogues are recombinant proteins making them easy and inexpensive to produce like all other recombinant proteins such as human growth factor (rHGH) or insulin. The preliminary evaluation of these analogues show stability at 40˚C for a week or longer with very little change in biological equivalence which facilitates transport and storage outside of the cold- chain required for many protein based therapeutics. They also withstood low pH conditions that resemble environments where they will be used as a prophylactic and be expected to maintain biological activity. A desired characteristic is that protection also be maintained for longer duration after a single dose. It appears that biological activity is suitable in that it is maintained for at least 24 hrs.
Both analogues tested show equivalent potency against viral replication as compared to PSC-RANTES invitro and in macaque challenge models. They achieve this in the same manner as PSC-RANTES by inhibiting the CCR5 receptor availability to the virus. One analogue causes the CCR5 receptor to sequester intracellularly but the other analogue doesn’t utilize this method and a mechanism was not described here. In the absence of a vaccine, the meaning of this very exciting discovery is enhanced due to the need of other avenues to slow the spread of virus. At the lecture, a recent study was also presented that statistically, we could treat out way out of this epidemic by affecting the spread of the disease. This is clearly a step in that direction while research to develop vaccines continue.

Cerini, Fabrice *; Landay, Alan PhD + ; Gichinga, Carolyne + ; Lederman, Michael M MD ++ ; Flyckt, Rebecca MD [S] ; Starks, David MD [S] ; Offord, Robin E PhD || ; Le Gal, Francois PhD [P]; Hartley, Oliver PhD * , Chemokine Analogues Show Suitable Stability for Development as Microbicides. J Aquir Defic Syndr. 2008;49;472-476.