Cytosolic delivery of viral nucleoprotein by listeriolysin O-liposome induces enhanced specific cytotoxic T lymphocyte response and protective immunity
被引:22
作者:
Mandal, Manas
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Univ Michigan, Coll Pharm, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USAUniv Michigan, Coll Pharm, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USA
Mandal, Manas
[1
]
Kawamura, Kim S.
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机构:
Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA
Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USAUniv Michigan, Coll Pharm, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USA
Kawamura, Kim S.
[2
,3
]
Wherry, E. John
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机构:
Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA
Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USAUniv Michigan, Coll Pharm, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USA
Wherry, E. John
[2
,3
]
Ahmed, Rafi
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机构:
Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA
Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USAUniv Michigan, Coll Pharm, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USA
Ahmed, Rafi
[2
,3
]
Lee, Kyung-Dall
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Univ Michigan, Coll Pharm, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USAUniv Michigan, Coll Pharm, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USA
Lee, Kyung-Dall
[1
]
机构:
[1] Univ Michigan, Coll Pharm, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USA
[2] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA
[3] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA
Cytotoxic T lymphocytes (CTLs) are capable of conferring protection against intracellular pathogens and tumor. Protective antiviral immunity, mediated by the activation of antigenic epitope-specific CTL, can be achieved by delivering exogenous antigen into the cytosol of antigen-presenting cells. Cytosolic introduction of vaccine antigen, however, requires a specialized delivery strategy due to the membrane barrier limiting the access of macromolecules to the cytosol. In this study, we have investigated the potential ability of listeriolysin O-containing liposomes (LLO-liposomes) to deliver lymphocytic choriomeningitis virus (LCMV) nucleoprotein (NP), harnessing the intracellular invasion mechanism of Listeria monocytogenes, to stimulate a INIP-specific CTL response. We have analyzed the ability of LLO-liposomes to induce an enhanced CTL response and determined the extent of CTL-mediated protection using an in vivo infection model. Mice immunized with LLO-liposomes containing NP generated a higher frequency of NP-specific CD8(+) T cells with greater effector activity than the control groups immunized with either non-LLO-liposomal NP or LLO-liposomes containing control protein. Moreover, LLO-liposomal NP-immunized mice were completely protected against a lethal intracerebral challenge with a virulent strain of LCMV and were capable of clearing a chronic LCMV infection. Our study demonstrates that LLO-liposomes can be used as an efficient vaccine delivery system carrying a viral antigenic protein to generate protective antiviral immunity.
机构:
SCRIPPS CLIN & RES FDN, DEPT IMMUNOL, 10666 N TORREY PINES RD, LA JOLLA, CA 92037 USASCRIPPS CLIN & RES FDN, DEPT IMMUNOL, 10666 N TORREY PINES RD, LA JOLLA, CA 92037 USA
KLAVINSKIS, LS
;
WHITTON, JL
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SCRIPPS CLIN & RES FDN, DEPT IMMUNOL, 10666 N TORREY PINES RD, LA JOLLA, CA 92037 USASCRIPPS CLIN & RES FDN, DEPT IMMUNOL, 10666 N TORREY PINES RD, LA JOLLA, CA 92037 USA
WHITTON, JL
;
OLDSTONE, MBA
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SCRIPPS CLIN & RES FDN, DEPT IMMUNOL, 10666 N TORREY PINES RD, LA JOLLA, CA 92037 USASCRIPPS CLIN & RES FDN, DEPT IMMUNOL, 10666 N TORREY PINES RD, LA JOLLA, CA 92037 USA
机构:
UNIV CALIF LOS ANGELES, SCH MED, DEPT MICROBIOL & IMMUNOL, LOS ANGELES, CA 90024 USAUNIV CALIF LOS ANGELES, SCH MED, DEPT MICROBIOL & IMMUNOL, LOS ANGELES, CA 90024 USA
LAU, LL
;
JAMIESON, BD
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UNIV CALIF LOS ANGELES, SCH MED, DEPT MICROBIOL & IMMUNOL, LOS ANGELES, CA 90024 USAUNIV CALIF LOS ANGELES, SCH MED, DEPT MICROBIOL & IMMUNOL, LOS ANGELES, CA 90024 USA
JAMIESON, BD
;
SOMASUNDARAM, T
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UNIV CALIF LOS ANGELES, SCH MED, DEPT MICROBIOL & IMMUNOL, LOS ANGELES, CA 90024 USAUNIV CALIF LOS ANGELES, SCH MED, DEPT MICROBIOL & IMMUNOL, LOS ANGELES, CA 90024 USA
SOMASUNDARAM, T
;
AHMED, R
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UNIV CALIF LOS ANGELES, SCH MED, DEPT MICROBIOL & IMMUNOL, LOS ANGELES, CA 90024 USAUNIV CALIF LOS ANGELES, SCH MED, DEPT MICROBIOL & IMMUNOL, LOS ANGELES, CA 90024 USA
机构:
SCRIPPS CLIN & RES FDN, DEPT IMMUNOL, 10666 N TORREY PINES RD, LA JOLLA, CA 92037 USASCRIPPS CLIN & RES FDN, DEPT IMMUNOL, 10666 N TORREY PINES RD, LA JOLLA, CA 92037 USA
KLAVINSKIS, LS
;
WHITTON, JL
论文数: 0引用数: 0
h-index: 0
机构:
SCRIPPS CLIN & RES FDN, DEPT IMMUNOL, 10666 N TORREY PINES RD, LA JOLLA, CA 92037 USASCRIPPS CLIN & RES FDN, DEPT IMMUNOL, 10666 N TORREY PINES RD, LA JOLLA, CA 92037 USA
WHITTON, JL
;
OLDSTONE, MBA
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h-index: 0
机构:
SCRIPPS CLIN & RES FDN, DEPT IMMUNOL, 10666 N TORREY PINES RD, LA JOLLA, CA 92037 USASCRIPPS CLIN & RES FDN, DEPT IMMUNOL, 10666 N TORREY PINES RD, LA JOLLA, CA 92037 USA
机构:
UNIV CALIF LOS ANGELES, SCH MED, DEPT MICROBIOL & IMMUNOL, LOS ANGELES, CA 90024 USAUNIV CALIF LOS ANGELES, SCH MED, DEPT MICROBIOL & IMMUNOL, LOS ANGELES, CA 90024 USA
LAU, LL
;
JAMIESON, BD
论文数: 0引用数: 0
h-index: 0
机构:
UNIV CALIF LOS ANGELES, SCH MED, DEPT MICROBIOL & IMMUNOL, LOS ANGELES, CA 90024 USAUNIV CALIF LOS ANGELES, SCH MED, DEPT MICROBIOL & IMMUNOL, LOS ANGELES, CA 90024 USA
JAMIESON, BD
;
SOMASUNDARAM, T
论文数: 0引用数: 0
h-index: 0
机构:
UNIV CALIF LOS ANGELES, SCH MED, DEPT MICROBIOL & IMMUNOL, LOS ANGELES, CA 90024 USAUNIV CALIF LOS ANGELES, SCH MED, DEPT MICROBIOL & IMMUNOL, LOS ANGELES, CA 90024 USA
SOMASUNDARAM, T
;
AHMED, R
论文数: 0引用数: 0
h-index: 0
机构:
UNIV CALIF LOS ANGELES, SCH MED, DEPT MICROBIOL & IMMUNOL, LOS ANGELES, CA 90024 USAUNIV CALIF LOS ANGELES, SCH MED, DEPT MICROBIOL & IMMUNOL, LOS ANGELES, CA 90024 USA