Evaluating the Compatibility of New Recombinant Protein Antigens (Trivalent NRRV) with a Mock Pentavalent Combination Vaccine Containing Whole-Cell Pertussis: Analytical and Formulation Challenges
dc.contributor.author | Kumar, Prashant | |
dc.contributor.author | Holland, David A. | |
dc.contributor.author | Secrist, Kathryn | |
dc.contributor.author | Taskar, Poorva | |
dc.contributor.author | Dotson, Brandy | |
dc.contributor.author | Saleh-Birdjandi, Soraia | |
dc.contributor.author | Adewunmi, Yetunde | |
dc.contributor.author | Doering, Jennifer | |
dc.contributor.author | Mantis, Nicholas J. | |
dc.contributor.author | Volkin, David B. | |
dc.contributor.author | Joshi, Sangeeta B. | |
dc.contributor.editor | Zhao, Aihua | |
dc.contributor.editor | Li, Junli | |
dc.date.accessioned | 2024-07-02T19:58:16Z | |
dc.date.available | 2024-07-02T19:58:16Z | |
dc.date.issued | 2024-06-03 | |
dc.identifier.citation | Kumar P, Holland DA, Secrist K, Taskar P, Dotson B, Saleh-Birdjandi S, Adewunmi Y, Doering J, Mantis NJ, Volkin DB, Joshi SB. Evaluating the Compatibility of New Recombinant Protein Antigens (Trivalent NRRV) with a Mock Pentavalent Combination Vaccine Containing Whole-Cell Pertussis: Analytical and Formulation Challenges. Vaccines (Basel). 2024 Jun 3;12(6):609. doi: 10.3390/vaccines12060609. PMID: 38932338; PMCID: PMC11209613. | en_US |
dc.identifier.uri | https://hdl.handle.net/1808/35298 | |
dc.description.abstract | Introducing new recombinant protein antigens to existing pediatric combination vaccines is important in improving coverage and affordability, especially in low- and middle-income countries (LMICs). This case-study highlights the analytical and formulation challenges encountered with three recombinant non-replicating rotavirus vaccine (NRRV) antigens (t-NRRV formulated with Alhydrogel® adjuvant, AH) combined with a mock multidose formulation of a pediatric pentavalent vaccine used in LMICs. This complex formulation contained (1) vaccine antigens (i.e., whole-cell pertussis (wP), diphtheria (D), tetanus (T), Haemophilus influenza (Hib), and hepatitis B (HepB), (2) a mixture of aluminum-salt adjuvants (AH and Adju-Phos®, AP), and (3) a preservative (thimerosal, TH). Selective, stability-indicating competitive immunoassays were developed to monitor binding of specific mAbs to each antigen, except wP which required the setup of a mouse immunogenicity assay. Simple mixing led to the desorption of t-NRRV antigens from AH and increased degradation during storage. These deleterious effects were caused by specific antigens, AP, and TH. An AH-only pentavalent formulation mitigated t-NRRV antigen desorption; however, the Hib antigen displayed previously reported AH-induced instability. The same rank-ordering of t-NRRV antigen stability (P[8] > P[4] > P[6]) was observed in mock pentavalent formulations and with various preservatives. The lessons learned are discussed to enable future multidose, combination vaccine formulation development with new vaccine candidates. | en_US |
dc.publisher | MDPI | en_US |
dc.rights | Copyright © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). | en_US |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_US |
dc.subject | Pediatric combination vaccine | en_US |
dc.subject | Aluminum-salt adjuvant | en_US |
dc.subject | Non-replicating rotavirus vaccine | en_US |
dc.subject | Diphtheria | en_US |
dc.subject | Tetanus | en_US |
dc.subject | Whole-cell pertussis | en_US |
dc.subject | Hepatitis B | en_US |
dc.subject | Haemophilus influenzae | en_US |
dc.subject | Formulation | en_US |
dc.subject | Compatibility | en_US |
dc.subject | Stability | en_US |
dc.subject | Preservatives | en_US |
dc.title | Evaluating the Compatibility of New Recombinant Protein Antigens (Trivalent NRRV) with a Mock Pentavalent Combination Vaccine Containing Whole-Cell Pertussis: Analytical and Formulation Challenges | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Kumar, Prashant | |
kusw.kuauthor | Holland, David A. | |
kusw.kuauthor | Secrist, Kathryn | |
kusw.kuauthor | Taskar, Poorva | |
kusw.kuauthor | Dotson, Brandy | |
kusw.kuauthor | Saleh-Birdjandi, Soraia | |
kusw.kuauthor | Adewunmi, Yetunde | |
kusw.kuauthor | Volkin, David B. | |
kusw.kuauthor | Joshi, Sangeeta B. | |
kusw.kudepartment | Department of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center | en_US |
dc.identifier.doi | 10.3390/vaccines12060609 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0003-2702-7038 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0001-8749-774X | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-5083-8640 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-1448-1998 | 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 | PMC11209613 | en_US |
dc.rights.accessrights | openAccess | en_US |
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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).