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Characterization of Co-Formulated High-Concentration Broadly Neutralizing Anti-HIV-1 Monoclonal Antibodies for Subcutaneous Administration
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 un...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551838/ https://www.ncbi.nlm.nih.gov/pubmed/32751063 http://dx.doi.org/10.3390/antib9030036 |
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author | Sharma, Vaneet K. Misra, Bijay McManus, Kevin T. Avula, Sreenivas Nellaiappan, Kaliappanadar Caskey, Marina Horowitz, Jill Nussenzweig, Michel C. Seaman, Michael S. Javeri, Indu Dey, Antu K. |
author_facet | Sharma, Vaneet K. Misra, Bijay McManus, Kevin T. Avula, Sreenivas Nellaiappan, Kaliappanadar Caskey, Marina Horowitz, Jill Nussenzweig, Michel C. Seaman, Michael S. Javeri, Indu Dey, Antu K. |
author_sort | Sharma, Vaneet K. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7551838 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75518382020-10-14 Characterization of Co-Formulated High-Concentration Broadly Neutralizing Anti-HIV-1 Monoclonal Antibodies for Subcutaneous Administration Sharma, Vaneet K. Misra, Bijay McManus, Kevin T. Avula, Sreenivas Nellaiappan, Kaliappanadar Caskey, Marina Horowitz, Jill Nussenzweig, Michel C. Seaman, Michael S. Javeri, Indu Dey, Antu K. Antibodies (Basel) Article 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. MDPI 2020-07-29 /pmc/articles/PMC7551838/ /pubmed/32751063 http://dx.doi.org/10.3390/antib9030036 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sharma, Vaneet K. Misra, Bijay McManus, Kevin T. Avula, Sreenivas Nellaiappan, Kaliappanadar Caskey, Marina Horowitz, Jill Nussenzweig, Michel C. Seaman, Michael S. Javeri, Indu Dey, Antu K. Characterization of Co-Formulated High-Concentration Broadly Neutralizing Anti-HIV-1 Monoclonal Antibodies for Subcutaneous Administration |
title | Characterization of Co-Formulated High-Concentration Broadly Neutralizing Anti-HIV-1 Monoclonal Antibodies for Subcutaneous Administration |
title_full | Characterization of Co-Formulated High-Concentration Broadly Neutralizing Anti-HIV-1 Monoclonal Antibodies for Subcutaneous Administration |
title_fullStr | Characterization of Co-Formulated High-Concentration Broadly Neutralizing Anti-HIV-1 Monoclonal Antibodies for Subcutaneous Administration |
title_full_unstemmed | Characterization of Co-Formulated High-Concentration Broadly Neutralizing Anti-HIV-1 Monoclonal Antibodies for Subcutaneous Administration |
title_short | Characterization of Co-Formulated High-Concentration Broadly Neutralizing Anti-HIV-1 Monoclonal Antibodies for Subcutaneous Administration |
title_sort | characterization of co-formulated high-concentration broadly neutralizing anti-hiv-1 monoclonal antibodies for subcutaneous administration |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551838/ https://www.ncbi.nlm.nih.gov/pubmed/32751063 http://dx.doi.org/10.3390/antib9030036 |
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