作者
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
发表日期
2021/3/1
期刊
Journal of pharmaceutical sciences
卷号
110
期号
3
页码范围
1042-1053
出版商
Elsevier
简介
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 …
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