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Cationic Liposomal Vaccine Adjuvant

Vaxjo ID 33
Vaccine Adjuvant Name Cationic Liposomal Vaccine Adjuvant
Adjuvant VO ID VO_0001262
Description Cationic liposomes are lipid-bilayer vesicles with a positive surface charge that have emerged as a promising new adjuvant technology having low toxicity and biodegradability (Ravindran et al., 2010). Cationic DSPC liposomes with cholesterol would not only deliver antigens more efficiently to the cytosol for eliciting a CD8+ T-cell response but would also have the added advantage of persistent antigen presentation through prolonged circulation, enabling the possibility of durable immunity induced by protein-based vaccination(Bhowmick et al., 2008).
Stage of Development Clinical Trial
Components Composed of stable liposomes formulated with distearoyl phosphatidylcholine (DSPC), a saturated phospholipid with a high transition temperature and with cholesterol, reduced clearance from blood and enhanced cationic lipid-mediated endosomal membrane destabilization (17, 73) (Bhowmick et al., 2008).
Dosage BALB/c mice were immunized by three intraperitoneal (i.p.) injections at 2-week intervals with graded doses entrapped in liposomes (200 µl) (Bhowmick et al., 2008).
Function Cationic liposomes have been shown to markedly potentiate activation of immune response to plasmid DNA and oligonucleotides. More recently, the induction of cell-mediated immune response to poorly immunogenic protein and peptide antigens has been made possible through the use of positively charged liposome carriers. Although these vesicles alone are relatively nonimmunogenic, their adjuvant potency toward the associated antigen is due in part to the efficient delivery of the antigen to professional antigen-presenting cells (APCs), including macrophages and dendritic cells. It is well established that liposomes channel protein and peptide antigens into the major histocompatibility complex class II pathways of APCs, resulting in enhanced antibody and antigen-specific T-cell proliferative response. In addition, there have been reports of the use of cationic liposomes for the generation of CD8+ T-cell response, which requires antigen presentation in the context of the major histocompatibility complex class I pathway (Bhowmick et al., 2008).
Safety Till date, liposomal vaccines against various diseases, such as cancer, HIV, Hepatitis B and malaria, have been investigated and found to be safe. However, their immunogenicity remains to be further improved. Although conventional liposomes are usually formulated with neutral and/or negatively charged lipids, many studies indicated that the cationic liposomes with positive surface charge more effectively enhanced Ag-specific immune response and promoted vaccine-induced anti-cancer responses than other liposomes. On the other hand, cationic liposomes at a high concentration significantly induced apoptosis of dendritic cells and suppressed immune response, suggesting the immunotoxic effect (Ma et al., 2009).
Related Vaccine(s)
References
Bhowmick et al., 2008: Bhowmick S, Ravindran R, Ali N. gp63 in stable cationic liposomes confers sustained vaccine immunity to susceptible BALB/c mice infected with Leishmania donovani. Infection and immunity. 2008; 76(3); 1003-1015. [PubMed: 18195029].
Christensen et al., 2011: Christensen D, Korsholm KS, Andersen P, Agger EM. Cationic liposomes as vaccine adjuvants. Expert review of vaccines. 2011; 10(4); 513-521. [PubMed: 21506648].
Ma et al., 2009: Yifan Ma; Dongmei Zhou; Xiaofang Xie; Bohan Dong; Yan Zhuang; Mingbin Zheng. A novel low-toxic liposomal adjuvant: Different liposome compositions regulate monocyte activation and viability. . November 2009; ; .
Ravindran et al., 2010: Ravindran R, Bhowmick S, Das A, Ali N. Comparison of BCG, MPL and cationic liposome adjuvant systems in leishmanial antigen vaccine formulations against murine visceral leishmaniasis. BMC microbiology. 2010; 10; 181. [PubMed: 20576102].