التفاصيل البيبلوغرافية
| العنوان: |
Stabilization and formulation of a recombinant Human Cytomegalovirus vector for use as a candidate HIV-1 vaccine. |
| المؤلفون: |
Kumru, Ozan S.1 (AUTHOR), Saleh-Birdjandi, Soraia1 (AUTHOR), Antunez, Lorena R.1 (AUTHOR), Sayeed, Eddy1 (AUTHOR), Robinson, David1 (AUTHOR), van den Worm, Sjoerd1 (AUTHOR), Diemer, Geoffrey S.1 (AUTHOR), Perez, Wilma1 (AUTHOR), Caposio, Patrizia1 (AUTHOR), Früh, Klaus1 (AUTHOR), Joshi, Sangeeta B.1 (AUTHOR), Volkin, David B.1 (AUTHOR) volkin@ku.edu |
| المصدر: |
Vaccine. Oct2019, Vol. 37 Issue 44, p6696-6706. 11p. |
| مصطلحات موضوعية: |
*HUMAN cytomegalovirus, *VIRAL vaccines, *TREHALOSE, *DEXTRAN, *FREEZE-thaw cycles, *VACCINES, *IONIC strength |
| مستخلص: |
Live attenuated viral vaccine/vector candidates are inherently unstable and infectivity titer losses can readily occur without defining appropriate formulations, storage conditions and clinical handling practices. During initial process development of a candidate vaccine against HIV-1 using a recombinant Human Cytomegalovirus vector (rHCMV-1), large vector titer losses were observed after storage at 4 °C and after undergoing freeze-thaw. Thus, the goal of this work was to develop candidate frozen liquid formulations of rHCMV-1 with improved freeze-thaw and short-term liquid stability for potential use in early clinical trials. To this end, a virus stability screening protocol was developed including use of a rapid, in vitro cell-based immunofluorescence focus assay to quantitate viral titers. A library of ∼50 pharmaceutical excipients (from various known classes of additives) were evaluated for their effect on vector stability after freeze-thaw cycling or incubation at 4 °C for several days. Certain additives including sugars and polymers (e.g., trehalose, sucrose, sorbitol, hydrolyzed gelatin, dextran 40) as well as removal of NaCl (lower ionic strength) protected rHCMV-1 against freeze-thaw mediated losses in viral titers. Optimized solution conditions (e.g., solution pH, buffers and sugar type) slowed the rate of rHCMV-1 titer losses in the liquid state at 4 °C. After evaluating various excipient combinations, three new candidate formulations were designed and rHCMV-1 stability was benchmarked against both the currently-used and a previously reported formulation. The new candidate formulations were significantly more stable in terms of reducing rHCMV-1 titer losses after 5 freeze-thaw cycles or incubation at 4 °C for 30 days. This case study highlights the utility of semi-empirical design of frozen liquid formulations of a live viral vaccine candidate, where protection against infectivity titer losses due to freeze-thaw and short-term liquid storage are sufficient to enable more rapid initiation of early clinical trials. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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