EFFECT OF ADJUVANTS ON IMMUNIZATION WITH DENGUE VIRUS-INDUCED CYTOTOXIC FACTOR

Specific active immunization with dengue type 2 virus (DV)-induced cyt okine, cytotoxic factor (CF), prevents CF-mediated pathology in mice. The present study was undertaken to determine the optimum dose of CF a nd the effect of different adjuvants on the immune response as assesse d by the study of anti-CF antibody titre by ELTSA and protection again st increase in capillary permeability to challenging dose of 3 mu g CF . The maximum protection of 94 +/- 4% against increase in capillary pe rmeability was observed at week 4 after immunization with 5 mu g dose of CF mixed with Freund's incomplete adjuvant (FIA), which gradually d ecreased to 21 +/- 10% on week 24. With a dose of 10 mu g the protecti on obtained was 79 +/- 5%, but persisted for a longer time at a higher level. The response was poor with 1 mu g dose of CF. The mean anti-CF antibody titres gradually decreased after reaching the peak at week 4 after immunization. Mice immunized with different adjuvants emulsifie d with 5 mu g CF were challenged at different intervals with 3 mu g CF . Maximum protection observed with CF + tetanus toroid (TT) and 84/245 was about 93 +/- 2% and 97 +/- 2%, while that with alhydrogel was 33 +/- 12% and with bacille Calmette-Guerin (BCG) was 67 +/- 4%. At week 24 after immunization, however, the best response was obtained with 10 mu g of adjuvant 84/246. Intracerebral challenge with 10 or 100 LD(50 ) dose of dengue type 2 virus showed significantly prolonged mean surv ival time and delayed onset of signs of sickness in immunized mice com pared with normal mice. The maximum survival time was with adjuvant 84 /246 even at week 24. The findings thus show that the optimum dose of CF is 5 mu g and the adjuvant of choice is 84/246.