Primary immune response to liposomal tetanus toxoid in mice: the effect of mediators.

Primary immune response (IgG1) to tetanus toxoid entrapped in liposomes composed of equimolar egg phosphatidylcholine and cholesterol, and the effect of a variety of physiological and non-physiological mediators (co-entrapped with the toxoid or entrapped in separate liposomes) on such responses, were studied in BALB/c mice. Results show that (i) primary responses, not detectable with the free antigen, were elicited with the same amount of antigen given in liposomes within a range (37.4:1-2857:1) of liposomal phospholipid to toxoid mass ratios. At a higher ratio (17,804:1) response was reduced to very low levels. Immune responses obtained with liposomal toxoid were maintained at measurable levels 24 weeks after immunization. (ii) Interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and N-acetyl muramyl-L-threonyl-D-isoglutamine ([Thr1]MDP), but not its liposoluble 6-O-stearoyl derivative (6-O-S-[Thr1]MDP), co-entrapped with the toxoid at appropriate phospholipid to toxoid ratios, generally reduced primary response to levels below those achieved with liposomes containing the antigen alone. Further, responses obtained with 6-O-S[Thr1]MDP coentrapped with the toxoid or separately entrapped were higher than those seen with [Thr1]MDP in similar formulations. The significance of these findings is discussed in conjunction with the structural characteristics of liposomes.