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Evaluating the Compatibility of New Recombinant Protein Antigens (Trivalent NRRV) with a Mock Pentavalent Combination Vaccine Containing Whole-Cell Pertussis: Analytical and Formulation Challenges
Kumar, Prashant Holland, David A. Secrist, Kathryn Taskar, Poorva Dotson, Brandy Saleh-Birdjandi, Soraia Adewunmi, Yetunde Doering, Jennifer Mantis, Nicholas J. Volkin, David B.
Kumar, Prashant
Holland, David A.
Secrist, Kathryn
Taskar, Poorva
Dotson, Brandy
Saleh-Birdjandi, Soraia
Adewunmi, Yetunde
Doering, Jennifer
Mantis, Nicholas J.
Volkin, David B.
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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.
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2024-06-03
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MDPI
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vaccines-12-00609.pdf
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Pediatric combination vaccine, Aluminum-salt adjuvant, Non-replicating rotavirus vaccine, Diphtheria, Tetanus, Whole-cell pertussis, Hepatitis B, Haemophilus influenzae, Formulation, Compatibility, Stability, Preservatives
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.