A newly engineered peptide 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, IBP-CP24 exhibited a prolonged half-life as well as potent and broad anti-HIV-1 activity, even against drug-resistant strains.
Enfuvirtide is the first anti-HIV peptide drug 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).
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. 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.
Funding: This work was supported by grants from the National Natural Science Foundation of China (81630090 to S.J.; 81672019, 81822045 and 81661128041 to L.L; 81703571 to W.X.; 81701998 to Q.W), National Megaprojects of China for Major Infectious Diseases (2018ZX10301403 to L.L.), U.S. NIH grants (AI127346 and DK119937 to L.S.), and a China Scholarship Council grant (File No. 201706100104 to W.B.). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Competing Interests: The authors have declared that no competing interests exist.
Citation: 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. https://doi.org/10.1371/journal.ppat.1008082
Key Laboratory of Medical Molecular Virology of MOE/NHC/CAMS, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai, China Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing
Key Laboratory for Animal Models of Emerging and Re-emerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, China
Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, United States of America
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