VACCINATION OF GENETICALLY SUSCEPTIBLE MICE AGAINST CHRONIC INFECTION WITH NEMATOSPIROIDES DUBIUS USING PERTUSSIGEN AS ADJUVANT

Abstract

Summary 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 >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 <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.

PROTECTIVE ANTIGENS IN FRACTIONS OF ADULT NEMATOSPIROIDES DUBIUS

“…Significant levels of protection can be achieved against Nematospiroides dubius in mice following vaccination with crude parasite extracts; up to 95^o protection was reported in genetically susceptible C57B1/6 mice (Mitchell and Munoz, 1983). In most other cases, however, the degree of protection achieved was much less (Cypess, 1970;Van Zandt, 1971;Goven and De Buysscher, 1980;Monroy et al, 1985).…”

“…Attempts to vaccinate mice against N. dubius using adult or larval homogenates have had varied success; this may relate to the influence of mouse genotype (Mitchell and Cruise, 1984), vaccination protocols (Cypess, 1970;Van Zandt, 1971;Goven and De Buysscher, 1980), type of adjuvant (Mitchell and Munoz, 1983), and route and mode of antigen presentation (Monroy et aL, 1985). However, in each case mice were protected to some extent, which indicates that there is the potential to develop a vaccine.…”

“…Defined protective antigens are essential for the development of efficacious vaccines. Mice are protected against A', dubius after immunization with crude worm extracts (Cypess, 1970;Van Zandt, 1971;Goven and De Buysscher, 1980;Mitchell and Munoz, 1983;Monroy et al, 1985). The protective antigens occur in both infective larvae (Jacobson, Brooks and Cypess, 1982;Benhke, Hannah and Pritchard, 1983) and in the soluble extracts of adult worms (Mitchell and Cruise, 1984;Monroy et al, 1985).…”

IMMUNIZATION WITH NEMATOSPIROIDES DUBIUS ADULT WORMS PLUS PERTUSSIGEN HAS DIFFERENT CONSEQUENCES IN MICE OF VARIOUS GENOTYPES

“…Two types of pertussigen-purified and crude-have been described in detail (Mitchell and Munoz. 1983).…”

“…standard error of the mean; Tn cell, thymus-derived helper cell for antibody production; w.o., weeks old. adjuvant, pertussigen, derived from Bordetetla pertussis (Mitchell and Munoz, 1983). This mouse strain was chosen in these vaccination studies because of evidence that it represents the extreme of genetically based susceptibility to chronic infection with A', chibius (Prowse and Mitchell, 1980).…”