Antibody and cytotoxic T-lymphocyte responses to a single liposome-associated peptide antigen

White, Wendy I.; Cassatt, David R.; Madsen, John W.; Burke, Steven J.; Woods, R. Claude; Wassef, Nabila M.; Alving, Carl R.; Koenig, Scott

doi:10.1016/0264-410x(94)00058-u

Cited by 69 publications

(46 citation statements)

References 45 publications

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“…Based on the previous successful induction of antibody and CTL responses to several L-encapsulated antigens containing lipid A (20,21,23,30), we hypothesized that our immunization strategy of delivering all EBO-Z proteins by encapsulating irradiated EBO-Z in L containing lipid A would provide protection against subsequent viral challenge. In the present study, mice immunized i.v.…”

Section: Discussionmentioning

confidence: 99%

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Induction of Immune Responses in Mice and Monkeys to Ebola Virus after Immunization with Liposome-Encapsulated Irradiated Ebola Virus: Protection in Mice Requires CD4 ⁺ T Cells

Rao

Bray²,

Alving

et al. 2002

J Virol

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Section: Discussionmentioning

confidence: 99%

“…We have previously shown that liposomes (L) serve as an efficient delivery system for a variety of antigens and evoke both types of immune response (2,28,30). L-encapsulated protein and peptide antigens enter the major histocompatibility complex (MHC) class I pathway and thus are efficient inducers of cytotoxic T lymphocytes (CTLs) (2,(18)(19)(20)(21)23).…”

mentioning

confidence: 99%

Induction of Immune Responses in Mice and Monkeys to Ebola Virus after Immunization with Liposome-Encapsulated Irradiated Ebola Virus: Protection in Mice Requires CD4 ⁺ T Cells

Rao

Bray²,

Alving

et al. 2002

J Virol

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“…Previous methods have involved using bacteria, viruses, adjuvants, or liposomes to introduce foreign molecules into the cell (6,7,20,21 The reduction in L. monocytogenes cfu isolated from vaccinated compared with nonvaccinated mice suggests that the anthrax toxin delivery system may have potential in vaccine development. In general, toxin-based systems may hold significant advantages over other systems for cytoplasmic delivery of CTL epitopes, including ones involving viruses, direct DNA injection, intracellular bacteria, or various adjuvants.…”

Section: Discussionmentioning

confidence: 99%

“…LFn-LL091-99 was amplified using an upstream primer that included (5' to 3') an NdeI site and sequence homologous to the 5' region of the LF gene. The downstream primer was homologous to the sequence encoding the last 6 amino acids of LFn and included (downstream of the homology) sequence encoding the LL091-99 epitope, sequence encoding stop codons, and a BamHI site. pXO1, the toxinencoding plasmid from Bacillus anthracis Sterne strain, was used as template.…”

mentioning

confidence: 99%

Anthrax toxin-mediated delivery of a cytotoxic T-cell epitope in vivo.

Ballard

Collier

Starnbach

1996

Proc. Natl. Acad. Sci. U.S.A.

123

105

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The protective antigen (PA) component of anthrax toxin mediates entry of the toxin's lethal factor (LF) and edema factor into the cytosolic compartment ofmammalian cells. The amino-terminal domain of LF (LFn; 255 amino acids) binds LF to PA, and when fused to heterologous proteins, the LFn domain delivers such proteins to the cytoplasm in the presence of PA. In the current study, we fused a 9-amino acid cytotoxic T-lymphocyte (CTL) epitope (LLO91-99) from an intracellular pathogen, Listeria monocytogenes, to LFn and measured the ability of the resulting LFn-LLO09199 fusion protein to stimulate a CTL response against the epitope in BALB/c mice. As little as 300 fmol of fusion could stimulate a response. The stimulation was PA-dependent and occurred with the peptide fused to either the amino terminus or the carboxyl terminus of LFn. Upon challenge with L. monocytogenes, mice previously injected with LFn-LL091-99 and PA showed a reduction of colony-forming units in spleen and liver, relative to nonimmunized control mice. These results indicate that anthrax toxin may be useful as a CTL-peptide delivery system for research and medical applications.All viruses and some bacterial and protozoan pathogens have evolved the ability to survive and replicate within mammalian cells. Immune recognition of these cytoplasmic pathogens depends upon the cell surface display of peptide antigens derived from pathogen-associated proteins. These peptides are presented in complexes with host class I molecules encoded by the major histocompatibility complex (MHC-I), and cytotoxic T lymphocytes (CTL) are activated following recognition of the foreign peptide in complex with MHC-I (1). Activated CTL lyse the infected cell, secrete cytokines, and then proliferate and differentiate (2, 3). Each of these steps plays an important role in clearing the host of the pathogen. Lysis of the target cell deprives the organism of its replicative niche and exposes the pathogen to elements of the humoral immune system. Secretion of cytokines has many effects, including enhancement of local immune responses. Proliferation of the CTL clone results in expansion of a set of reactive CTL to effect clearance of the pathogen from other infected cells, whereas differentiation provides a set of long-lived memory cells available to respond more quickly and effectively to subsequent challenge. Vaccines that prime these memory cells provide protection of the host upon reexposure to the pathogen.For a vaccine to mimic infection by cytoplasmic pathogens, it must introduce the target antigen(s) into the cytosol of host cells in vivo. This has been accomplished by expressing heterologous antigens by live viral or bacterial vectors, by using adjuvants, or by delivering DNA expression vectors (DNA vaccines) (4-7). Herein we describe a strategy for introducing CTL epitopes into the cytosol of host cells, in vivo, using delivery components of an intracellularly acting toxin, anthrax toxin.

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“…Unfortunately, each of these systems contains its own unique set of problems and is not always suitable for all individuals (18)(19)(20)(21). Particularly, in the case of HIV-1 and its macaque close cousin simian immunodeficiency virus (SIV), live attenuated virus has been shown to protect adult monkeys from a subsequent challenge with virulent virus (22), but the safety of an attenuated strain, especially in newborns, has been questioned (23).…”

mentioning

confidence: 99%

Targeting HIV proteins to the major histocompatibility complex class I processing pathway with a novel gp120-anthrax toxin fusion protein

Goletz

Klimpel

Arora

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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A challenge for subunit vaccines whose goal is to elicit CD8 ؉ cytotoxic T lymphocytes (CTLs) is to deliver the antigen to the cytosol of the living cell, where it can be processed for presentation by major histocompatibility complex (MHC) class I molecules. Several bacterial toxins have evolved to efficiently deliver catalytic protein moieties to the cytosol of eukaryotic cells. Anthrax lethal toxin consists of two distinct proteins that combine to form the active toxin. Protective antigen (PA) binds to cells and is instrumental in delivering lethal factor (LF) to the cell cytosol. To test whether the lethal factor protein could be exploited for delivery of exogenous proteins to the MHC class I processing pathway, we constructed a genetic fusion between the amino-terminal 254 aa of LF and the gp120 portion of the HIV-1 envelope protein. Cells treated with this fusion protein (LF254-gp120) in the presence of PA effectively processed gp120 and presented an epitope recognized by HIV-1 gp120 V3-specific CTL. In contrast, when cells were treated with the LF254-gp120 fusion protein and a mutant PA protein defective for translocation, the cells were not able to present the epitope and were not lysed by the specific CTL. The entry into the cytosol and dependence on the classical cytosolic MHC class I pathway were confirmed by showing that antigen presentation by PA ؉ LF254-gp120 was blocked by the proteasome inhibitor lactacystin. These data demonstrate the ability of the LF amino-terminal fragment to deliver antigens to the MHC class I pathway and provide the basis for the development of novel T cell vaccines.

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Antibody and cytotoxic T-lymphocyte responses to a single liposome-associated peptide antigen

Cited by 69 publications

References 45 publications

Induction of Immune Responses in Mice and Monkeys to Ebola Virus after Immunization with Liposome-Encapsulated Irradiated Ebola Virus: Protection in Mice Requires CD4 ⁺ T Cells

Induction of Immune Responses in Mice and Monkeys to Ebola Virus after Immunization with Liposome-Encapsulated Irradiated Ebola Virus: Protection in Mice Requires CD4 ⁺ T Cells

Anthrax toxin-mediated delivery of a cytotoxic T-cell epitope in vivo.

Targeting HIV proteins to the major histocompatibility complex class I processing pathway with a novel gp120-anthrax toxin fusion protein

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Antibody and cytotoxic T-lymphocyte responses to a single liposome-associated peptide antigen

Cited by 69 publications

References 45 publications

Induction of Immune Responses in Mice and Monkeys to Ebola Virus after Immunization with Liposome-Encapsulated Irradiated Ebola Virus: Protection in Mice Requires CD4 + T Cells

Induction of Immune Responses in Mice and Monkeys to Ebola Virus after Immunization with Liposome-Encapsulated Irradiated Ebola Virus: Protection in Mice Requires CD4 + T Cells

Anthrax toxin-mediated delivery of a cytotoxic T-cell epitope in vivo.

Targeting HIV proteins to the major histocompatibility complex class I processing pathway with a novel gp120-anthrax toxin fusion protein

Contact Info

Product

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Induction of Immune Responses in Mice and Monkeys to Ebola Virus after Immunization with Liposome-Encapsulated Irradiated Ebola Virus: Protection in Mice Requires CD4 ⁺ T Cells

Induction of Immune Responses in Mice and Monkeys to Ebola Virus after Immunization with Liposome-Encapsulated Irradiated Ebola Virus: Protection in Mice Requires CD4 ⁺ T Cells