Effect of adjuvants on immunization with dengue virus-induced cytotoxic factor

Abstract

Specific active immunization with dengue type 2 virus (DV)-induced cytokine. cytotoxic factor (CF), prevents CF-mediated pathology in mice. The present study was undertaken to determine the optimum dose of CF and the effect of different adjuvants on the immune response as assessed by the study of anti-CF antibody titre by ELISA and protection against increase in capillary permeability to challenging dose of 3 µ g CF. The maximum protection of 94 ± 4% against increase in capillary permeability was observed at week 4 after immunization with 5 µ g dose of CF mixed with Freund's incomplete adjuvant (FIA), which gradually decreased to 21 ± 10% on week 24. With a dose of 10 µ g the protection obtained was 79± 5%, but persisted for a longer time at a higher level. The response was poor with 1 µ 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 emulsified with 5µ g CF were challenged at different intervals with 3µ g CF. Maximum protection observed with CF + tetanus toxoid (TT) and 84/246 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 10µ g of adjuvant 84/246. Intracerebral challenge with 10 or 100 LD dose of dengue type 2 virus showed significantly prolonged mean survival time and delayed onset of signs of sickness in immunized mice compared 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 µ g and the adjuvant of choice is 84/246.