Vaccination of genetically susceptible mice against chronic infection with Nematospiroides dubius using pertussigen as adjuvant.

Abstract

The intestinal nematode Nematospiroides dubius persists for prolonged periods in mice after a single oral administration of infective larvae. After multiple administrations of larvae, some inbred mouse strains (termed 'resistant') develop the capacity to expel the majority of adult worms from the intestines. Other mouse strains such as CBA/H and C57BL/6 (and, in particular, males) are far more susceptible in that they expel few, if any, adult worms after repeated doses of larvae and may die with high worm burdens. One means to accelerate rejection of adult worms in a primary infection is to presensitize mice with a small number of living adult worms injected intraperitoneally. However, an impressive vaccination effect of ectopically implanted worms has only been demonstrated to date in resistant mouse strains. In this paper, success has been achieved in vaccinating genetically susceptible mice against chronic primary infection with N. dubius. Young male specific pathogen-free (SPF)-derived C57BL/6 mice demonstrate greater than 90% resistance after injection of adult worms but only when further injected with pertussigen from Bordetella pertussis as adjuvant. Accelerated rejection of adult worms appears to be the principal manifestation of resistance in vaccinated mice. A high degree of protection has also been obtained in recipients of pertussigen plus the supernatant of a crude worm extract equivalent to less than 10 adult worms per mouse. Although no information is available on the effector mechanisms responsible for worm rejection in vaccinated mice, pertussigen is known to increase both immediate and delayed type hypersensitivity responses and to increase tissue sensitivity to histamine. A strategy which sensitizes recipients such that a subsequent challenge infection is not sustained, and which is effective in highly susceptible hosts, opens the way to vaccination against chronic intestinal infections in those hosts most in need of protection.