dc.contributor.author | Kumar, Prashant | |
dc.contributor.author | Shukla, Ravi S. | |
dc.contributor.author | Patel, Ashaben | |
dc.contributor.author | Pullagurla, Swathi R. | |
dc.contributor.author | Bird, Christopher | |
dc.contributor.author | Ogun, Oluwadara | |
dc.contributor.author | Kumru, Ozan S. | |
dc.contributor.author | Hamidi, Ahd | |
dc.contributor.author | Hoeksema, Femke | |
dc.contributor.author | Yallop, Christopher | |
dc.contributor.author | Bines, Julie E. | |
dc.contributor.author | Joshi, Sangeeta B. | |
dc.contributor.author | Volkin, David B. | |
dc.date.accessioned | 2022-01-17T22:28:37Z | |
dc.date.available | 2022-01-17T22:28:37Z | |
dc.date.issued | 2021-04-16 | |
dc.identifier.citation | Kumar, P., Shukla, R. S., Patel, A., Pullagurla, S. R., Bird, C., Ogun, O., Kumru, O. S., Hamidi, A., Hoeksema, F., Yallop, C., Bines, J. E., Joshi, S. B., & Volkin, D. B. (2021). Formulation development of a live attenuated human rotavirus (RV3-BB) vaccine candidate for use in low- and middle-income countries. Human vaccines & immunotherapeutics, 17(7), 2298–2310. https://doi.org/10.1080/21645515.2021.1885279 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/32422 | |
dc.description.abstract | Formulation development was performed with the live, attenuated, human neonatal rotavirus vaccine candidate (RV3-BB) with three main objectives to facilitate use in low- and middle- income countries including (1) a liquid, 2–8°C stable vaccine, (2) no necessity for pre-neutralization of gastric acid prior to oral administration of a small-volume dose, and (3) a low-cost vaccine dosage form. Implementation of a high-throughput RT-qPCR viral infectivity assay for RV3-BB, which correlated well with traditional FFA assays in terms of monitoring RV3-BB stability profiles, enabled more rapid and comprehensive formulation development studies. A wide variety of different classes and types of pharmaceutical excipients were screened for their ability to stabilize RV3-BB during exposure to elevated temperatures, freeze-thaw and agitation stresses. Sucrose (50–60% w/v), PEG-3350, and a solution pH of 7.8 were selected as promising stabilizers. Using a combination of an in vitro gastric digestion model (to mimic oral delivery conditions) and accelerated storage stability studies, several buffering agents (e.g., succinate, adipate and acetate at ~200 to 400 mM) were shown to protect RV3-BB under acidic conditions, and at the same time, minimize virus destabilization during storage. Several optimized RV3-BB candidate formulations were identified based on negligible viral infectivity losses during storage at 2–8°C and −20°C for up to 12 months, as well as by relative stability comparisons at 15°C and 25°C (up to 12 and 3 months, respectively). These RV3-BB stability results are discussed in the context of stability profiles of other rotavirus serotypes as well as future RV3-BB formulation development activities. | en_US |
dc.publisher | Taylor and Francis | en_US |
dc.rights | © 2021 The Author(s). Published with license by Taylor & Francis Group, LLC. This is an Open Access article distributed under the terms of the Creative Commons Attribution License. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.subject | Rotavirus | en_US |
dc.subject | RV3-BB | en_US |
dc.subject | Live virus vaccine | en_US |
dc.subject | Formulation | en_US |
dc.subject | Stability | en_US |
dc.subject | Oral delivery | en_US |
dc.title | Formulation development of a live attenuated human rotavirus (RV3-BB) vaccine candidate for use in low- and middle-income countries | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Kumar, Prashant | |
kusw.kuauthor | Shukla, Ravi S. | |
kusw.kuauthor | Patel, Ashaben | |
kusw.kuauthor | Pullagurla, Swathi R. | |
kusw.kuauthor | Bird, Christopher | |
kusw.kuauthor | Ogun, Oluwadara | |
kusw.kuauthor | Kumru, Ozan S. | |
kusw.kuauthor | Joshi, Sangeeta B. | |
kusw.kuauthor | Volkin, David B. | |
kusw.kudepartment | Pharmaceutical Chemistry | en_US |
dc.identifier.doi | 10.1080/21645515.2021.1885279 | en_US |
kusw.oaversion | Scholarly/refereed, publisher version | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC8189091 | en_US |
dc.rights.accessrights | openAccess | en_US |