Results from the Acanthocheilonema viteae /jird model screen
for potentially protective filarial antigens
by Richard Lucius
To test the protective potential of recombinant O. volvulus antigens,
a rodent model for filariasis was optimized, and we are now midway through
the first vaccinations with a cocktail of recombinant proteins. Previous
work had demonstrated that immunization with irradiation attenuated L3 of
A. viteae, a rodent filariid infecting the jird (Meriones unguiculatus),
induces nearly complete resistance to challenge infection. A significant
factor in this process are the secretory antigens of L3 since immunization
with culture supernatants of L3 consistently induced 50-60% protection.
The first task was to find an optimal immunization scheme using our secreted
antigens as a model substance.
In order to determine the best route for administration of antigens, animals
were first immunized with secretory antigens by intradermal, subcutaneous,
intraperitoneal, intramuscular, and intravenous application. The animals
tolerated the treatments well, but, they did not exhibit protective responses
when compared to the controls. A possible explanation for this may have
been the different jird strain utilized in this trial; therefore, the experiment
will be repeated with an appropriate strain of animals.
In a subsequent experiment, the effect of various adjuvants was tested
by subcutaneous immunization (which had been used successfully in previous
tests) with L3 culture supernatants. The results indicated that one adjuvant
(RIBI) interfered negatively with the immune response of the animals since
worm burdens of immunized animals were significantly higher than in the
control group. Following immunization with the purified plant saponin adjuvant
QS21 (from Cambridge Biosciences), animals harboured significantly fewer
worms than the control group (56% protection). Immunization with the adjuvants
STP (sqaulene. tween, pleuronic) and BCG, as well as with two different
block copolymers (water/oil adjuvants supplied by Robert Hunter of Cytrx
Corporation) did not induce significant protection; however, trends towards
protection (33-52%) were observed.
In December, jird groups were immunized with the same cocktail of five
recombinant antigens (OV7, paramyosin, C27, RAL2, and OI3) together with
five of the adjuvants mentioned above as used in David Abraham's mouse/chamber
model. In this way, the consistency between the mouse/chamber model and
the jird model can be determined.