Negatively Charged Liposomes Show Potent Adjuvant Activity When Simply Admixed with Protein Antigens

Abstract

Liposomes have been investigated extensively as a vaccine delivery system. Herein the adjuvant activities of liposomes with different net surface charges (neutral, positive, or negative) were evaluated when admixed with protein antigens, ovalbumin (OVA, pI = 4.7), Bacillus anthracis protective antigen protein (PA, pI = 5.6), or cationized OVA (cOVA). Mice immunized subcutaneously with OVA admixed with different liposomes generated different antibody responses. Interestingly, OVA admixed with net negatively charged liposomes prepared with DOPA was as immunogenic as OVA admixed with positively charged liposomes prepared with DOTAP. Immunization of mice with the anthrax PA protein admixed with the net negatively charged DOPA liposomes also induced a strong and functional anti-PA antibody response. When the cationized OVA was used as a model antigen, liposomes with net neutral, negative, or positive charges showed comparable adjuvant activities. Immunization of mice with the OVA admixed with DOPA liposomes also induced OVA-specific CD8+ cytotoxic T lymphocyte responses and significantly delayed the growth of OVA-expressing B16-OVA tumors in mice. However, not all net negatively charged liposomes showed a strong adjuvant activity. The adjuvant activity of the negatively charged liposomes may be related to the liposome’s ability (i) to up-regulate the expression of molecules related to the activation and maturation of antigen-presenting cells and (ii) to slightly facilitate the uptake of the antigens by antigen-presenting cells. Simply admixing certain negatively charged liposomes with certain protein antigens of interest may represent a novel platform for vaccine development.

Adjuvant formulation structure and composition are critical for the development of an effective vaccine against tuberculosis

“…Based on this we were surprised that the anionic liposome formulation of GLA provided the greatest enhancement of ID93-specific TH1 responses, even though there was little detectable association with ID93. However another study found that anionic liposomes, such as the DPPG-containing liposomes used here, are effective adjuvant formulations despite lack of antigen association [43]. The mechanisms of this activity are unclear but may affect the site of vaccine injection or cells that traffic to the injection site and take up the antigen.…”

Liposomes as vaccine delivery systems: a review of the recent advances

“…Interestingly, OVA admixed with negative 1,2-dioleyl-sn-glycero-3-phosphatidic acid liposomes was as immunogenic as OVA admixed with positive 1,2-dioleoyl-3-trimethyl ammonium propane liposomes. The cOVA antigen showed comparable adjuvant activities in all liposomes [Yanasarn et al 2011]. Neutral phosphatidylcholine (PC)/cholesterol small unilamellar vesicles (SUV) also proved to be effective vaccine carriers.…”

Liposomal Drug Delivery: A Versatile Platform for Challenging Clinical Applications

“…Lipoplexes may also act as immuneadjuvant when admixed with protein antigens. However, their adjuvant activity is primarily due to enhanced uptake of proteins by antigen presenting cells as compared to negatively charged liposomes that promote activation and maturation of antigen presenting cells (128). Recent research has focused on making lipoplexes more plasma friendly, optimizing morphological features which can control cellular uptake and intracellular disposition (129)(130).…”