Source: Thailand Medical News Dec 06, 2019 5 years, 2 weeks, 3 days, 4 hours, 22 minutes ago
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.
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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
