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Rapid Developability Assessments to Formulate Recombinant Protein Antigens as Stable, Low-Cost, Multi-Dose Vaccine Candidates: Case-Study With Non-Replicating Rotavirus (NRRV) Vaccine Antigens

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Rapid Developability Assessments to Formulate Recombinant Protein Antigens as Stable, Low-Cost, Multi-Dose Vaccine Candidates: Case-Study With Non-Replicating Rotavirus (NRRV) Vaccine Antigens

Journal of Pharmaceutical Sciences

Fecha de publicación: 4 de diciembre de 2020

DOI: https://doi.org/10.1016/j.xphs.2020.11.039

Autores: Nishant Sawant, Kawaljit Kaur, David A. Holland, John M. Hickey, Sanjeev Agarwal, Joseph R. Brady, Neil C. Dalvie, Mary Kate Tracey, M. Lourdes Velez-Suberbie, Stephen A. Morris, Shaleem I. Jacob, Daniel G. Bracewell, Tarit K. Mukhopadhyay, Kerry R. Love, J. Christopher Love, Sangeeta B. Joshi, David B. Volkin

Background: A two-step developability assessment workflow is described to screen variants of recombinant protein antigens under various formulation conditions to rapidly identify stable, aluminum-adjuvanted, multi-dose vaccine candidates. For proof-of-concept, a series of sequence variants of the recombinant non-replicating rotavirus (NRRV) P[8] protein antigen (produced in Komagataella phaffii) were compared in terms of primary structure, post-translational modifications, antibody binding, conformational stability, relative solubility and preservative compatibility. Based on these results, promising P[8] variants were down-selected and the impact of key formulation conditions on storage stability was examined (e.g., presence or absence of the aluminum-adjuvant Alhydrogel and the preservative thimerosal) as measured by differential scanning calorimetry (DSC) and antibody binding assays. Good correlations between rapidly-generated developability screening data and storage stability profiles (12 weeks at various temperatures) were observed for aluminum-adsorbed P[8] antigens. These findings were extended and confirmed using variants of a second NRRV antigen, P[4].

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