title: Incompatibility of lyophilized inactivated polio vaccine with liquid pentavalent whole-cell-pertussis-containing vaccine.
abstract: A hexavalent vaccine containing diphtheria toxoid, tetanus toxoid, whole cell pertussis, Haemophilius influenza type B, hepatitis B and inactivated polio vaccine (IPV) may: (i) increase the efficiency of vaccination campaigns, (ii) reduce the number of injections thereby reducing needlestick injuries, and (iii) ensure better protection against pertussis as compared to vaccines containing acellular pertussis antigens. An approach to obtain a hexavalent vaccine might be reconstituting lyophilized polio vaccine (IPV-LYO) with liquid pentavalent vaccine just before intramuscular delivery. The potential limitations of this approach were investigated including thermostability of IPV as measured by D-antigen ELISA and rat potency, the compatibility of fluid and lyophilized IPV in combination with thimerosal and thimerosal containing hexavalent vaccine. The rat potency of polio type 3 in IPV-LYO was 2 to 3-fold lower than standardized on the D-antigen content, suggesting an alteration of the polio type 3 D-antigen particle by lyophilization. Type 1 and 2 had unaffected antigenicity/immunogenicity ratios. Alteration of type 3 D-antigen could be detected by showing reduced thermostability at 45°C compared to type 3 in non-lyophilized liquid controls. Reconstituting IPV-LYO in the presence of thimerosal (TM) resulted in a fast temperature dependent loss of polio type 1-3 D-antigen. The presence of 0.005% TM reduced the D-antigen content by ∼20% (polio type 2/3) and ∼60% (polio type 1) in 6h at 25°C, which are WHO open vial policy conditions. At 37°C, D-antigen was diminished even faster, suggesting that very fast, i.e., immediately after preparation, intramuscular delivery of the conceived hexavalent vaccine would not be a feasible option. Use of the TM-scavenger, l-cysteine, to bind TM (or mercury containing TM degradation products), resulted in a hexavalent vaccine mixture in which polio D-antigen was more stable.
authors.affiliation: Intravacc (Institute for Translational Vaccinology), Antonie van Leeuwenhoeklaan 9, P.O. Box 450, 3720 AL Bilthoven, The Netherlands.
authors.forename: Heleen
authors.initials: H
authors.lastname: Kraan
authors.affiliation: Intravacc (Institute for Translational Vaccinology), Antonie van Leeuwenhoeklaan 9, P.O. Box 450, 3720 AL Bilthoven, The Netherlands. Electronic address: rimko.ten.have@intravacc.nl.
authors.forename: Rimko
authors.initials: R
authors.lastname: Ten Have
authors.affiliation: Intravacc (Institute for Translational Vaccinology), Antonie van Leeuwenhoeklaan 9, P.O. Box 450, 3720 AL Bilthoven, The Netherlands.
authors.forename: Larissa
authors.initials: L
authors.lastname: van der Maas
authors.affiliation: Intravacc (Institute for Translational Vaccinology), Antonie van Leeuwenhoeklaan 9, P.O. Box 450, 3720 AL Bilthoven, The Netherlands; Division of Drug Delivery Technology, Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands.
authors.forename: Gideon
authors.initials: G
authors.lastname: Kersten
authors.affiliation: Intravacc (Institute for Translational Vaccinology), Antonie van Leeuwenhoeklaan 9, P.O. Box 450, 3720 AL Bilthoven, The Netherlands. Electronic address: jp.amorij@virtuvax.nl.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Amorij
mesh_terms: D000818:Animals; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000276:immunology; D005612:Freeze Drying; D018073:Haemophilus Vaccines / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000276:immunology; D000071497:Immunogenicity, Vaccine; D011054:Poliovirus Vaccine, Inactivated / Q000276:immunology*; D051381:Rats; D013696:Temperature; D013849:Thimerosal / Q000737:chemistry; D064166:Vaccine Potency
chemical_list: D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; D017325:Hepatitis B Vaccines; D011054:Poliovirus Vaccine, Inactivated; C122182:diphtheria-tetanus-acellular pertussis-Hib-hepatitis B vaccine; D013849:Thimerosal
keywords: Hexavalent vaccine; Inactivated polio vaccine; Lyophilization; Rat potency; Thimerosal