A DNA Vaccine Prime Followed by a Liposome-Encapsulated Protein Boost Confers Enhanced Mucosal Immune Responses and Protection

Yang, Kun; Whalen, Barbara J.; Tirabassi, Rebecca S.; Selin, Liisa K.; Levchenko, Tatyana; Torchilin, Vladimir P.; Kislauskis, Edward H.; Guberski, Dennis L.

doi:10.4049/jimmunol.180.9.6159

Cited by 32 publications

(27 citation statements)

References 59 publications

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“…The advantages of this approach include potential synergistic effects on the induction of an immune response and the generation of a robust T cell-mediated immune response [42]. In the present study, we have used a DNA prime and protein boost protocol to investigate the immunogenicity of a model antigen expressed from a DNA-based vaccine delivered via LLO-LPDII.…”

Section: Discussionmentioning

confidence: 99%

Enhanced in vivo gene expression mediated by listeriolysin O incorporated anionic LPDII: Its utility in cytotoxic T lymphocyte-inducing DNA vaccine

Sun

Provoda

Lee

2010

Journal of Controlled Release

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Enhanced in vivo gene expression using non-viral vectors is a critical issue in gene therapy in general. Among the many potential utilities of non-viral vector-mediated gene delivery, its application in DNA-based vaccination is an attractive approach with several practical advantages over conventional vaccination. We have previously shown that the endosomolytic bacterial protein listeriolysin O (LLO) is capable of facilitating transfection in vitro using the LPDII (anionic liposome-polycation-DNA complexes) delivery system. In the present study we have extended and investigated the DNA delivery of LLO-containing LPDII to in vivo and evaluated its utility in DNA vaccination in mice. We further investigated the ability of this non-viral gene delivery system to elicit an immune response to a model antigen ovalbumin (OVA), particularly focusing on the OVA-specific CD8+ cytotoxic T lymphocyte (CTL) response, after delivery of a plasmid containing the OVA cDNA. A DNA prime and protein boost protocol was employed to generate cytotoxic T cell responses. Our results show that increased in vitro and in vivo transfection efficiencies were observed when LLO was incorporated into LPDII. This LLO-LPDII formulation produced an enhanced functional antigen-specific CD8+ T cell response in vivo compared to the heat-inactivated LLO-containing LPDII (HI-LLO-LPDII) formulation. Furthermore, a significantly higher CTL frequency was observed in the splenocytes isolated from the mice primed with LLO-LPDII by an enzyme-linked immunosorbent spot assay. Interferon-γ production upon specific stimulation by OVA-specific CD8+ peptide was also significantly stronger with the inclusion of LLO into LPDII. These findings suggest that the LLO-containing LPDII system possesses noteworthy potential as a candidate carrier for DNA vaccine delivery.

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Section: Discussionmentioning

confidence: 99%

Enhanced in vivo gene expression mediated by listeriolysin O incorporated anionic LPDII: Its utility in cytotoxic T lymphocyte-inducing DNA vaccine

Sun

Provoda

Lee

2010

Journal of Controlled Release

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“…The aqueous space in most liposomal structures allows the incorporation of hydrophilic antigens. Thus, preparation of liposomes by addition of aqueous solution of antigens to dried lipid films resulting in multilamellar vesicles (MLV) is the conventional and most favored method of liposome preparation for vaccine formulations (Afrin and Ali 1997;Yang et al 2008). Another method used for insertion of antigens in liposomes is through direct insertion of proteins anchored by GPI of biological membrane into vesicles already formed and with high efficiency of incorporation ).…”

Section: New Perspectives For Applications Of Proteoliposomesmentioning

confidence: 99%

Proteoliposomes in nanobiotechnology

et al. 2012

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Proteoliposomes are systems that mimic lipid membranes (liposomes) to which a protein has been incorporated or inserted. During the last decade, these systems have gained prominence as tools for biophysical studies on lipid-protein interactions as well as for their biotechnological applications. Proteoliposomes have a major advantage when compared with natural membrane systems, since they can be obtained with a smaller number of lipidic (and protein) components, facilitating the design and interpretation of certain experiments. However, they have the disadvantage of requiring methodological standardization for incorporation of each specific protein, and the need to verify that the reconstitution procedure has yielded the correct orientation of the protein in the proteoliposome system with recovery of its functional activity. In this review, we chose two proteins under study in our laboratory to exemplify the steps necessary for the standardization of the reconstitution of membrane proteins in liposome systems: (1) alkaline phosphatase, a protein with a glycosylphosphatidylinositol anchor, and (2) Na,K-ATPase, an integral membrane protein. In these examples, we focus on the production of the specific proteoliposomes, as well as on their biochemical and biophysical characterization, with emphasis on studies of lipid-protein interactions. We conclude the chapter by highlighting current prospects of this technology for biotechnological applications, including the construction of nanosensors and of a multiprotein nanovesicular biomimetic to study the processes of initiation of skeletal mineralization.

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“…such as vaccinia virus and adenovirus vectors) have been developed to enhance systemic immune responses. To raise potent humoral and T cell-mediated immune responses systemically and at mucosal surfaces, Yang et al developed a mucosal immunization regimen that avoids the use of viral vectors and bacterial toxin-based adjuvants yet induces potent immune responses both systemically and mucosally [47]. Using hepatitis B surface Ag (HBsAg), i.m.…”

Section: Mucosal Immunization Strategies Against Rsv Infectionmentioning

confidence: 99%

“…When an intranasal live virus challenge with a recombinant vaccinia virus expressing HBsAg was administered, immunized mice were completely protected without exhibiting lung pathology. This immunization strategy was also successful in raising synergistic immune responses systemically and mucosally in both adult and neonatal mice [45]. …”

Section: Mucosal Immunization Strategies Against Rsv Infectionmentioning

confidence: 99%

“…Recent work has indicated that a significant benefit of a DNA vaccine prime followed by a protein boost is a dramatic improvement in the quality of the antibody response [49–52]. It would be very interesting to test if a heterologous DNA prime and liposomal protein boost strategy [44,47] is capable of inducing RSV antigen-specific mucosal immune responses and protection to a level higher than that of natural infection.…”

Section: Mucosal Immunization Strategies Against Rsv Infectionmentioning

confidence: 99%

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Mucosal vaccines against respiratory syncytial virus

Yang

Varga

2014

Current Opinion in Virology

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Respiratory syncytial virus (RSV) is a leading cause of severe respiratory disease in infants, young children, immune-compromised and elderly populations worldwide. Natural RSV infection in young children does not elicit long-lasting immunity and individuals remain susceptible to repeated RSV infections throughout life. Because RSV infection is restricted to the respiratory tract, an RSV vaccine should elicit mucosal immunity at upper and lower respiratory tracts in order to most effectively prevent RSV reinfection. Although there is no safe and effective RSV vaccine available, significant progress has been recently made in basic RSV research and vaccine development. This review will discuss recent advances in the identification of a new neutralizing antigenic site within the RSV fusion (F) protein, understanding the importance of mucosal immune responses against RSV infection, and the development of novel mucosal vaccination strategies.

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A DNA Vaccine Prime Followed by a Liposome-Encapsulated Protein Boost Confers Enhanced Mucosal Immune Responses and Protection

Cited by 32 publications

References 59 publications

Enhanced in vivo gene expression mediated by listeriolysin O incorporated anionic LPDII: Its utility in cytotoxic T lymphocyte-inducing DNA vaccine

Enhanced in vivo gene expression mediated by listeriolysin O incorporated anionic LPDII: Its utility in cytotoxic T lymphocyte-inducing DNA vaccine

Proteoliposomes in nanobiotechnology

Mucosal vaccines against respiratory syncytial virus

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