Characterization of Co-Formulated High-Concentration Broadly Neutralizing Anti-HIV-1 Monoclonal Antibodies for Subcutaneous Administration.
Vaneet K SharmaBijay MisraKevin T McManusSreenivas AvulaKaliappanadar NellaiappanMarina CaskeyJill HorowitzMichel C NussenzweigMichael S SeamanIndu JaveriAntu K DeyPublished in: Antibodies (Basel, Switzerland) (2020)
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.
Keyphrases
- human immunodeficiency virus
- antiretroviral therapy
- hiv positive
- hiv infected
- hepatitis c virus
- hiv testing
- hiv aids
- men who have sex with men
- ms ms
- simultaneous determination
- south africa
- drug delivery
- mass spectrometry
- risk assessment
- solid phase extraction
- climate change
- high resolution
- liquid chromatography
- gene expression
- tandem mass spectrometry
- human health
- quantum dots
- sensitive detection