Immunomodulating properties of two synthetic adjuvants: Dependence upon type of antigen, dose, and time of administration

Abstract

The effects of two synthetic adjuvants on the antibody response to sheep red blood cells (SRBC) as a thymus dependent (TD) antigen and to dinitropheny&s-Ficoll as a thymus-independent (TI-1) antigen were investigated in mice. Both dimethyldioctadecylammonium bromide (DDA) and dextran sulfate (DXS) augmented the humoral response to SRBC but not to dinitrophenylJgFicoll if injected simultaneously with antigen. Dose-response curves of both antigen and adjuvant revealed that DXS compared to DDA is a more effective adjuvant for the induction of a humoral response to SRBC. Intraperitoneal injection of DDA or DXS evoked a sequence of distinct immune responsive states in mice, measured by the capacity to develop an anti-SRBC response. A short immune-potentiating period (~6 hr) is followed by a suppressive, second immunepotentiating state. The immune suppressive state lasted for a period of about 8 days and was restricted to TD-antigens. Suppression could be totally overridden by injection of DDA or DXS simultaneously with antigen, suggesting that the suppressive state was reversible. The kinetics of the observed alteration of the immune response by DDA and DXS were very similar. It is concluded that differences in the modulation of the immune response by DDA and DXS are limited to the initial state. Long-term effects like the induction of a succession of distinct immune responsive states, are more or less similar for both adjuvants. Possible mechanisms by which these immunomodulators interfere with the immune system are discussed.

Anti‐inflammatory activity of cationic lipids

“…injection of cationic lipids showed defective secretion of NO and TNF‐α when activated by LPS. Hilgers et al (1984) have also shown that the i.p. injection of positively charged liposomes can modulate the immune system.…”

Adjuvant effects of dimethyl dioctadecyl ammonium bromide, complete Freund's adjuvant and aluminium hydroxide on neutralizing antibody, antibody-isotype and delayed-type hypersensitivity responses to Semliki Forest virus in mice

“…However, binding of DDA to antigens is not always essential for its adjuvant activity. Interaction with macrophages brings about release of cytokines (including interferon), depresses antigen degradation and prolongs antigen persistence [20,21,25,34]. Moreover, since isotype switching and DTH, which are affected by DDA so efficiently, are both dependent on the TH1 subset of T helper cells through the production of IL-2 and interferon y [35] it can be assumed that DDA has a direct or an indirect influence on those lymphocytes.…”

“…In an investigation for the evaluation of adjuvant activities of aliphatic nitrogenous bases several substances possessed immunostimulating effects and amongst them was a quaternary ammonium lipoid compound, dimethyl dioctadecyl ammonium chloride (DDA) [16]. The adjuvanticity of the bromide derivative of this substance was extensively tested in a variety of laboratory animals in combination with proteins and haptens [16][17][18], red blood cells [19][20][21] tumour cells [22] and viruses [23][24][25][26][27]. DDA was also tried in humans in conjunction with tetanus toxoid vaccines [28,29].…”

Comparison of dimethyl dioctadecyl ammonium bromide, Freund's complete adjuvant and mineral oil for induction of humoral antibodies, cellular immunity and resistance to Newcastle disease virus in chickens

“…As already discussed in our previous paper [10] there is no agreement as to the exact mechanism of action of DDA. One group of authors mantains that the adjuvanticity of DDA is independent of the presence of antigen [20][21][22][23] while others have shown the importance of direct binding of the antigen to DDA or simultaneous addition of the DDA and antigen at the same inoculation site [24][25][26]. In the present study, DDA vaccines which contained NDV antigen preparations of different purities were compared ( Table 3).…”