Synergistic teratogenic effect produced in mice by whole cell pertussis vaccine

Pertussis whole cell bacterial vaccine was injected in mice during early pregnancy to disclose any teratogenic effect on the brain of the fetuses. Cytochalasin D by itself induced exencephaly in a dose dependent way in fetal mice. When pregnant mice received a single injection of pertussis vaccine on day 8 of gestation and a subteratogenic dose of cytochalasin D on days 8, 9 and 10 of gestation a synergistic teratogenic action of pertussis vaccine and cytochalasin D in mice was observed. When autopsy was performed after a further 9 to 10 days a significant number of brain malformations was found. In order to analyse which component in the vaccine might be responsible for the co-teratogenic effect, purified pertussis components, pertussis toxin and filamentous haemagglutinin were used in combination with cytochalasin D, but no malformations occurred. The same results were obtained by using diphtheria-tetanus-polio (DiTePol) vaccine and acellular pertussis component vaccine, whereas the use of whole cell typhoid vaccine resulted in a high rate of fetuses with exencephalies. Experiments with purified Bordetella pertussis and Escherichia coli lipopolysaccharides indicated that lipopolysaccharides in whole cell pertussis vaccine as well as in typhoid vaccine were the factors causing teratogenicity in fetal mice.