Update on the Mouse/Chamber Vaccine Model
by David Abraham
The diffusion chamber/mouse model was used to answer several questions
regarding the induction of protective immunity to larval Onchocerca volvulus.
The first question related to the route of administration of immunizations.
Mice were immunized subcutaneously, intraperitoneally, or intramuscularly
with a killed preparation of O. volvulus third-stage larvae (L3).
A reduction in the survival of challenge L3 of approximately 60% was seen
regardless of the route of administration of the vaccine.
The second question addressed concurred the choice of adjuvant to be used
with the recombinant antigens. To answer this question 5 recombinant antigens
(OI3, OV7, C27, paramyosin, and RAL2) were selected based on their occurrence
in L3. These antigens were combined at equal concentrations into a cocktail
which was then used with 4 different adjuvants to test the effect that the
adjuvants had on the development of protective immunity. Immunization with
the cocktail of antigens with the adjuvants Ribi, BCG, and QS21 (a plant
saponin adjuvant; Cambridge Biosciences) did not induce protective immunity.
Immunization, however, with the antigens with the adjuvant block copolymer
(Robert Hunter, Cytrx Corporation) using the water in oil formulation (BCWO)
caused a 67% reduction in challenge parasite survival.
It was of interest to note that the percent eosinophils and the absolute
number of eosinophils found in the diffusion chambers of animals immunized
with antigen and BCWO was higher than in animals which had not been immunized
or that had been inoculated with BCWO without antigen. Evidence is accumulating
in the mouse-chamber model system that eosinophils are an integral component
of the protective immune response. Therefore, the finding of elevated eosinophil
numbers only in diffusion chambers recovered from animals immunized with
antigen and BCWO suggests that the finding of a decrease in parasite survival
in these animals was not an experimental artifact but was, indeed, a manifestation
of a protective immune response.
A second trial was set up to test two formulations of the block copolymer,
water in oil vs. oil in water, for their relative efficacies. This experiment
failed to demonstrate statistical difference between control and immunized
groups because of large variations in parasite recovery within all of the
groups, although the appropriate trends were seen. We are currently retesting
the two adjuvant systems and will then proceed to testing individual antigens
with the adjuvant system of choice.