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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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.
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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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