Thailand HIV News
By reengineering a peptide called CP24
, the new compound called IBP-CP24
has the potential to be further developed as a long-acting anti-HIV
drug that can be used alone or in combination with a broad neutralizing antibody for the treatment and prevention of HIV
-1 infection, according to a study published December 5 in the open-access journal PLOS Pathogens
by Lu Lu and Shibo Jiang of Fudan University and Lishan Su of the University of North Carolina at Chapel Hill, and colleagues.
As reported in the study, the newly reengineered result, IBP-CP24 exhibited a prolonged half-life as well as potent and broad anti-HIV
-1 activity, even against drug-resistant strains.
The first anti-HIV
peptide drug, Enfuvirtide was approved by the U.S. Food and Drug Administration. However, its clinical application is limited because of its short half-life and the emergence of enfuvirtide-resistant HIV
strains. In the new study, researchers developed a novel strategy to prolong the half-life of a short anti-HIV
peptide called CP24
by fusing it to the human Immunoglobulin G (IgG) Fc-binding peptide (IBP).
The new compound, IBP-CP24
inhibited a broad spectrum of HIV
-1 strains, including those resistant to enfuvirtide. Most importantly, its half-life in the blood of rhesus monkeys was 46.1 h, approximately 26- and 14-fold longer than that of CP24
and enfuvirtide, respectively. IBP-CP24
intravenously administered in rhesus monkeys did not induce significant IBP-CP24
-specific antibody response and showed no obvious toxicity.
The researchers told Thailand Medical
News that mice pretreated with IBP-CP24
were protected from HIV
-1 infection, and co-administration of IBP-CP24
and normal human IgG in mice with chronic HIV
-1 infection resulted in a significant decrease in viruses in the bloodstream. Interestingly, the combined use of IBP-CP24
and a broad HIV
neutralizing antibody showed a synergistic anti-HIV
-1 effect, suggesting that this strategy may reduce the dose of the antibody and peptide and the cost of treatment.
Reference : Bi W, Xu W, Cheng L, Xue J, Wang Q, Yu F, et al. (2019) IgG Fc-binding motif-conjugated HIV-1 fusion inhibitor exhibits improved potency and in vivo half-life: Potential application in combination with broad neutralizing antibodies. PLoS Pathog 15(12): e1008082. doi.org/10.1371/journal.ppat.1008082