| Autor: |
Sharma VK; IAVI, 125 Broad Street, New York, NY 10004, USA., Misra B; CuriRx, Inc., 205 Lowell Street, Wilmington, MA 01887, USA., McManus KT; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA., Avula S; IAVI, 125 Broad Street, New York, NY 10004, USA., Nellaiappan K; CuriRx, Inc., 205 Lowell Street, Wilmington, MA 01887, USA., Caskey M; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA., Horowitz J; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA., Nussenzweig MC; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.; Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA., Seaman MS; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA., Javeri I; CuriRx, Inc., 205 Lowell Street, Wilmington, MA 01887, USA., Dey AK; IAVI, 125 Broad Street, New York, NY 10004, USA. |
| Abstrakt: |
The discovery of numerous potent and broad neutralizing antibodies (bNAbs) against Human Immunodeficiency Virus type 1 (HIV-1) envelope glycoprotein has invigorated the potential of using them as an effective preventative and therapeutic agent. The majority of the anti-HIV-1 antibodies, currently under clinical investigation, are formulated singly for intra-venous (IV) infusion. However, due to the high degree of genetic variability in the case of HIV-1, a single broad neutralizing antibody will likely not be sufficient to protect against the broad range of viral isolates. To that end, delivery of two or more co-formulated bnAbs against HIV-1 in a single subcutaneous (SC) injection is highly desired. We, therefore, co-formulated two anti-HIV bnAbs, 3BNC117-LS and 10-1074-LS, to a total concentration of 150 mg/mL for SC administration and analyzed them using a panel of analytical techniques. Chromatographic based methods, such as RP-HPLC, CEX-HPLC, SEC-HPLC, were developed to ensure separation and detection of each antibody in the co-formulated sample. In addition, we used a panel of diverse pseudoviruses to detect the functionality of individual antibodies in the co-formulation. We also used these methods to test the stability of the co-formulated antibodies and believe that such an approach can support future efforts towards the formulation and characterization of multiple high-concentration antibodies for SC delivery. |
