NIDDK IN VIVO EFFICACY OF FC-BISPECIFICS STUDY

As part of the statutorily required functions of the National Institute of Health (NIH), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) conducts and supports a wide range of biomedical research directly through intramural research within NIH laboratories, and externally through grants to universities and other medical research institutions across the country. In addition, NIDDK supports research training for students and scientists at various stages of their careers and a range of education and outreach programs to bring science-based information to patients and their families, health care professionals, and the public.

Within the Laboratory of Bioorganic Chemistry, NIDDK, the Natural Products Chemistry Section (NPCS) requires studies to determine the in vivo anti- human immunodeficiency virus (HIV) and immune-recruiting activity of a novel panel of antibody or Fc-lectin/nanobody conjugates (termed antibody-protein conjugates or APC’s). These studies are being performed with optimized APCs that have been shown to prevent HIV infection in cell-based and vivo studies. The research study is needed to expand a recent pilot study in humanized CD34+ mice (strain NOD- Prkdcem26Cd52Il2rgem26Cd22 /NjuCrl). The protocols used will measure antiviral efficacy of the APCs in both pre-infection and post-infection studies. Viral infection will be measured by polymerase chain reaction (PCR) and flow cytometry of T-cells in infected and control mice. In-life blood collections will be conducted on study dates every 2 weeks (W#):  -1 day (W0), W2, W4, S6 and W8 (end-point) or +1 day (W0), W2, W4, S6 and W8 (end-point). A terminal blood collection will be conducted on day 56 for all mice. Blood processing and serum preparations will be conducted on all samples. Additionally, PCR and flow cytometry will be conducted. A total of six study groups comprising six CD34+ mice per group will be used for testing of five APCs plus vehicle control.

The NPCS carries out research aimed at developing antiviral antibody-protein conjugates with an emphasis on anti-HIV conjugates that offer durable protection. This is a long-term project that has been funded by the Office of AIDS Research. Previous studies tested plasma stability and toxicity (pharmacokinetics) of conjugate mGRFT-Fc(glyc). Favorable results showing protection and recruitment of immune/cytotoxic antiviral responses in APCs containing a glycosylated Fc region indicate the need for expanded testing.