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.