Synergistic Effects of Synthetic Adjuvants on the Humoral Immune Response

Abstract

The effect of combinations of adjuvants on the humoral immune response to sheep red blood cells (SRBC) as antigen was investigated. Adjuvants belonging to two categories differing in physicochemical properties were used: surfactants (N, N-dioctadecyl-N′, N′-bis-(2-hydroyethyl)propanediamine (CP-20,961), dimethyldioctadecylammonium bromide (DDA), neutrally charged liposomes, polyol (L 101 and L 121) and polyanions [dextran sulfate (DXS), liquoid and suramine]. All adjuvants but suramine augmented humoral responses to 2 × 10⁷ SRBC measured by the number of direct anti-SRBC plaque-forming cells (PFC) in the spleen. The response to 2 × 10⁶ SRBC was enhanced considerably by L 121 and DXS but hardly or not at all by the other adjuvants. Combinations of two adjuvants were made at distinct ratios (1:3, 2:2, and 3:1) and injected intraperitoneally with 2 × 10⁶ SRBC. Low responses (5 × 10³ PFC per spleen) were induced by combinations of liquoid or suramine with DDA or DXS, and by combinations of CP-20,961 liposomes, L 101 or L 121 with DDA. Combinations of the surfactants DDA, CP-20,961, liposomes, L 101 or L 121 with DXS evoked responses which were significantly higher than the sum of responses supported by the single adjuvants. Ratios of 1:3 or 2:2 (surfactant: DXS) resulted in the most effective combinations. The data obtained suggest that only adjuvants derived from two different physicochemical groups are able to act synergistically.

Bilayer-Forming Synthetic Lipids: Drugs or Carriers?

“…Therefore, in-vivo DODAB cytotoxicity was expected to be none so that the in-vivo effects could be ascribed only to AB [255]. Nevertheless, DODAB as a carrier in-vivo, was very successful, e.g., for presenting antigen as an excellent immunoadjuvant [161,166].…”