Liposomes as immunological adjuvants in eliciting antibodies specific to the synthetic polypeptide poly(LTyr, LGlu)‐poly(DLAla)–poly(LLys) with high frequency of site‐associated idiotypic determinants

Abstract

The antibody response to the synthetic polypeptide, poly(LTyr, LGlu)-poly(DLAla)--poly(LLys), [(T,G)-A--L], injected entrapped in liposomes which served as adjuvant has been analyzed. The liposomes used were composed of phosphatidylcholine, cholesterol, dicetylphosphate and DL alpha-tocopherol (molar ratios as 4:3:0.1:0.5) and therefore, were negatively charged. Since the (T,G)-A--L is also negatively charged, no free complexes were formed. The (T,G)-A--L was found to be entrapped inside the enclosed volume of the liposomes, and no (T,G)-A--L antigenic determinants could be detected on the liposomal membranes. Injection of high-responder C3H.SW (H-2b) mice with (T,G)-A--L-bearing liposomes demonstrated that the i.p. and the i.v. routes of immunization were efficient in eliciting (T, G)-A--L specific antibodies, whereas the i.d. injection led to poor antibody responses. The latter route of immunization is the most effective when (T,G)-A--L is injected in complete Freund's adjuvant (CFA). When low doses (0.1 and 1 microgram) of (T, G)-A--L were used for immunization, the liposomes were better adjuvants than CFA. The effectiveness of the liposomes as immunological adjuvants was also shown in their ability to induce high-potential, primed memory cells. The pattern of low (H-2k,a) and high (H-2b) responsiveness to (T,G)-A--L was retained following immunization with (T,G)-A--L entrapped in liposomes, as tested in two pairs of congenic strains. (T,G)-A--L-specific antibodies induced by injection with 1 microgram antigen entrapped in liposomes bear the (T,G)-A--L site-related idiotypic markers of C3H.SW (Igh-1a) mice in a significantly higher frequency than the homologous idiotypes, namely the antibodies elicited in this strain against (T,G)-A--L in CFA. Thus, liposomes may serve as adjuvants for the production of relatively restricted (T,G)-A--L-specific antibodies of high quality.

Liposomes as Carriers of Peptide Antigens: Induction of Antibodies and Cytotoxic T Lymphocytes to Conjugated and Unconjugated Peptides

“…Immunization with proteoliposomes containing a fusion protein derived from influenza virus also have reportedly caused directed targeting of an SIV nine amino acid gag p27 peptide into the intracellular class I MHC presentation pathway, resulting in generation of cytotoxic T lymphocytes (Miller et al 1992). Two early reports suggested that liposomes might serve as vehicles for immunizing with unconjugated large polypeptides, or even peptides, without the addition of further adjuvants (Lifshitz et al 1981, Dreesman et al 1982. Because of the promising results that we obtained after immunizing with liposome-encapsulated NANP-albumin conjugate without additional adjuvant (Alving et al 1986) (viJe supra) we have undertaken a series of experiments to investigate whether liposomes containing unconjugated or lipid-conjugated synthetic peptides might be useful either for producing unique antibody specificities or for constructing practical vaccines (Ogert et al 1990, White et al 1995, Yasutomi et al 1995a.b, Glenn et al 1995.…”

Use of reconstituted influenza virus virosomes as an immunopotentiating delivery system for a peptide-based vaccine

“…While proteins reconstituted into phospholipid bilayers have been shown to be effective antigens, the ability of liposomes containing no viral proteins to potentiate the immune response to peptides has been less impressive. Often the liposome±peptide complex has to be emulsi®ed in an adjuvant in order to elicit antibody production [26,27]. IRIV have already been shown to act as an ef®cient and highly effective means of enhancing the immune response to a variety of vaccine antigens, thus illustrating their broad suitability as a vaccine delivery system.…”

Allergen Entrapped in Liposomes Reduce Allergenicity and Induce Immunogenicity on Repeated Injections in Mice

“…Water-soluble substances can be entrapped in the aqueous compartment of the vesi cles. The immunopotentiating effect of liposomes was reported by Allison and Gregoriadis [5], Subsequent studies by various co-workers confirmed the adjuvant activity of liposomes in case of various protein anti gens [6][7][8][9], peptides [10] and lipid antigens [11]. Gre goriadis and Allison [12] have demonstrated, using diptheria toxoid, that the primary immune response to entrapped protein was not abolished, but occur rence of allergic reaction upon repeated challenge with entrapped antigen was prevented.…”