TY - JOUR
T1 - Immunostimulatory and antigen delivery properties of liposomes made up of total polar lipids from non-pathogenic bacteria leads to efficient induction of both innate and adaptive immune responses
AU - Faisal, Syed M.
AU - Chen, Jenn wei
AU - McDonough, Sean P.
AU - Chang, Chao Fu
AU - Teng, Ching Hao
AU - Chang, Yung Fu
N1 - Funding Information:
This work was supported in part by the Biotechnology Research and Development Corporation (BRDC) , the Harry M. Zweig Memorial Fund for Equine Research , the New York State Science and Technology Foundation and Center of Advanced Technology (CAT) . We would like to thank Dr. Rodman Getchell (Department of Microbiology and Immunology) for assistance in Auto MACS, 7500 Sequence Detector and FACS analysis.
Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2011/3/16
Y1 - 2011/3/16
N2 - Novel liposomes prepared from total polar lipids of non-pathogenic bacteria, viz. Leptospira biflexa serovar Potac (designated leptosomes) and Mycobacterium smegmatis (designated smegmosomes) were evaluated for their adjuvant effects with various antigen presenting cells (APCs), viz. murine macrophage cell line, J774A.1 and bone marrow derived dendritic cells (BMDCs). These liposomes induced strong membrane fusion as evident from resonance energy transfer (RET) assays and effectively transferred the fluorescent probe to the membrane of these APCs. Moreover, both vesicles caused significant activation of APCs as revealed by release of proinflammatory cytokines (IL-6, IL-12, TNF-α) and enhanced expression of co-stimulatory signals and maturation markers (CD80, CD86, MHCII), which was significantly higher for smegmosomes as compared to leptosomes. Additionally, activation of APCs by liposomes correlated with their ability to stimulate allospecific T cell proliferation and IFN-γ release. In contrast, conventional PC/chol liposomes failed to fuse and induced only a very low level of APC activation. Interestingly, the stimulatory activity of these lipid vesicles was restricted to APCs as they did not cause any significant activation or mitogenic effect on lymphocytes (B and T cells) in vitro. Overall, the activation of APCs by both leptosomes and smegmosomes correlated with activation of strong humoral and cell mediated immune responses in C57/BL6 mice to entrapped ovalbumin (OVA) and was significantly higher than those induced by conventional liposomes and alum, which failed to activate cytotoxic T lymphocytes (CTLs). Taken together these results demonstrate the adjuvant potential of these novel lipid vesicles that may simultaneously induce both innate and adaptive immune responses due to their immune stimulatory and antigen delivery properties.
AB - Novel liposomes prepared from total polar lipids of non-pathogenic bacteria, viz. Leptospira biflexa serovar Potac (designated leptosomes) and Mycobacterium smegmatis (designated smegmosomes) were evaluated for their adjuvant effects with various antigen presenting cells (APCs), viz. murine macrophage cell line, J774A.1 and bone marrow derived dendritic cells (BMDCs). These liposomes induced strong membrane fusion as evident from resonance energy transfer (RET) assays and effectively transferred the fluorescent probe to the membrane of these APCs. Moreover, both vesicles caused significant activation of APCs as revealed by release of proinflammatory cytokines (IL-6, IL-12, TNF-α) and enhanced expression of co-stimulatory signals and maturation markers (CD80, CD86, MHCII), which was significantly higher for smegmosomes as compared to leptosomes. Additionally, activation of APCs by liposomes correlated with their ability to stimulate allospecific T cell proliferation and IFN-γ release. In contrast, conventional PC/chol liposomes failed to fuse and induced only a very low level of APC activation. Interestingly, the stimulatory activity of these lipid vesicles was restricted to APCs as they did not cause any significant activation or mitogenic effect on lymphocytes (B and T cells) in vitro. Overall, the activation of APCs by both leptosomes and smegmosomes correlated with activation of strong humoral and cell mediated immune responses in C57/BL6 mice to entrapped ovalbumin (OVA) and was significantly higher than those induced by conventional liposomes and alum, which failed to activate cytotoxic T lymphocytes (CTLs). Taken together these results demonstrate the adjuvant potential of these novel lipid vesicles that may simultaneously induce both innate and adaptive immune responses due to their immune stimulatory and antigen delivery properties.
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U2 - 10.1016/j.vaccine.2011.01.110
DO - 10.1016/j.vaccine.2011.01.110
M3 - Article
C2 - 21300103
AN - SCOPUS:79952363514
VL - 29
SP - 2381
EP - 2391
JO - Vaccine
JF - Vaccine
SN - 0264-410X
IS - 13
ER -
