Mucosal Adjuvant Properties of the<i>Shigella</i>Invasin Complex

Kaminski, Robert W.; Turbyfill, K. Ross; Oaks, Edwin V.

doi:10.1128/iai.74.5.2856-2866.2006

Cited by 33 publications

(24 citation statements)

References 51 publications

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“…Invaplex also has inherent adjuvant properties (15), which are likely due to the native biological activities of the major antigenic components. The IpaB and IpaC proteins are used by wild-type shigellae to induce actin polymerization, phagocytosis, and eventual escape from phagolysosomes (reviewed in reference 43).…”

Section: Oaks Unpublished Results)mentioning

confidence: 99%

“…In addition, the LPS component of the complex likely engages TLR-4 on APCs, such as resident macrophages, beginning a cascade of events culminating in the release of chemokines and cytokines and eventual recruitment of additional APCs to the site of immunization. By potentially functioning as both an immunomodulator and as a vaccine delivery system, Invaplex has augmented the immunogenicity of several codelivered heterologous protein antigens, including ovalbumin and the protective antigen from Bacillus anthracis (15), colonization factors from enterotoxigenic E. coli (32), and a recombinant Campylobacter sp. FlaA protein (14).…”

Section: Oaks Unpublished Results)mentioning

confidence: 99%

“…Five mice per group were boosted on day 56 with an intranasal immunization of purified recombinant Sta56 protein (r56Karp; 15 g) combined with Invaplex 50 (5 g). Vaccine formulations (total volume, 25 l) were delivered intranasally as previously described (15). Research was conducted in compliance with the Animal Welfare Act and other federal statutes and regulations relating to animals and experiments involving animals and adhered to principles stated in the National Research Council's 1996 Guide for the Care and Use of Laboratory Animals (28).…”

Section: Methodsmentioning

confidence: 99%

“…Invaplex consists of the invasion plasmid antigen (Ipa) proteins IpaB and IpaC, in a native complex with Shigella lipopolysaccharide (LPS). After intranasal immunization of mice (46) or guinea pigs (31) with Invaplex, mucosal and systemic immune responses directed to the Ipa proteins and LPS are induced (15) and the resulting immune response is protective against challenge with virulent shigellae in animal models (31). Furthermore, phase 1 clinical studies in humans indicate that Invaplex is both safe and immunogenic, inducing a potent mucosal immune response (R. W. Kaminski and E. V.…”

mentioning

confidence: 99%

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Mucosal Adjuvanticity of a Shigella Invasin Complex with DNA-Based Vaccines

Kaminski

Turbyfill

Chao

et al. 2009

Clin Vaccine Immunol

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Protection against many infectious diseases may require the induction of cell-mediated and mucosal immunity. Immunization with plasmid DNA-based vaccines has successfully induced cell-mediated immune responses in small animals but is less potent in humans. Therefore, several methods are under investigation to augment DNA vaccine immunogenicity. In the current study, a mucosal adjuvant consisting of an invasin protein-lipopolysaccharide complex (Invaplex) isolated from Shigella spp. was evaluated as an adjuvant for DNA-based vaccines. Coadministration of plasmid DNA encoding the Orientia tsutsugamushi r56Karp protein with Invaplex resulted in enhanced cellular and humoral responses in intranasally immunized mice compared to immunization with DNA without adjuvant. Mucosal immunoglobulin A, directed to plasmid-encoded antigen, was detected in lung and intestinal compartments after Invaplex-DNA immunization followed by a protein booster. Moreover, immunization with Invaplex elicited Shigella-specific immune responses, highlighting its potential use in a combination vaccine strategy. The capacity of Invaplex to enhance the immunogenicity of plasmid-encoded genes suggested that Invaplex promoted the uptake and expression of the delivered genes. To better understand the native biological activities of Invaplex related to its adjuvanticity, interactions between Invaplex and mammalian cells were characterized. Invaplex rapidly bound to and was internalized by nonphagocytic, eukaryotic cells in an endocytic process dependent on actin polymerization and independent of microtubule formation. Invaplex also mediated transfection with several plasmid DNA constructs, which could be inhibited with monoclonal antibodies specific for IpaB and IpaC or Invaplex-specific polyclonal sera. The cellular binding and transport capabilities of Invaplex likely contribute to the adjuvanticity and immunogenicity of Invaplex.Immunization with plasmid DNA encoding vaccine antigens holds the promise of inducing cell-mediated and humoral immunity while offering several advantages over traditional immunization technologies, including ease of production, low cost, and the ability to engineer a highly defined product (10). However, several obstacles must be overcome prior to the widespread use of DNA vaccines. For example, although potent cell-mediated and humoral responses have been induced in small animal models, the success of DNA-based vaccines in humans is limited (22). The modest immune responses elicited in humans have highlighted the need for methods to enhance the immunogenicity of DNA-based vaccines. Inducing antigenspecific immune responses after plasmid DNA immunization is dependent on either in vivo transfection of antigen-presenting cells (APCs), expression of intracellular peptide and presentation in major histocompatibility complex (MHC) class I by transfected nonprofessional APCs, or presentation of phagocytosed antigen, exported from transfected cells, in MHC class I or class II by APCs (6). Thus, several approaches have been used ...

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Section: Oaks Unpublished Results)mentioning

confidence: 99%

Section: Oaks Unpublished Results)mentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Mucosal Adjuvanticity of a Shigella Invasin Complex with DNA-Based Vaccines

Kaminski

Turbyfill

Chao

et al. 2009

Clin Vaccine Immunol

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“…Nasal and fecal samples were assessed by ELISA for anti-S. flexneri 2a LPS and anti-S. flexneri 2a Invaplex 50 IgA titers as previously described [16,23] with minor modifications. First, total IgA in stool extracts and nasal extracts was determined by a capture ELISA [24] using goat anti-human F(ab ) 2 (Jackson Laboratories) as capture antibody and HRP conjugated goat anti-human IgA (KPL, Rockville, MD) as the detecting antibody.…”

Section: Determination Of Antibody Titers In Plasma and Mucosal Samplesmentioning

confidence: 99%

Safety and immunogenicity of an intranasal Shigella flexneri 2a Invaplex 50 vaccine

Riddle¹,

Kaminski²,

Williams³

et al. 2011

Vaccine

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Results: There were no serious adverse events and the majority of adverse events (98%) were mild. Antibody secreting cells (ASC), plasma, and mucosal immune responses to Shigella antigens were detected at all three dose levels with the 690 g dose inducing the highest magnitude and frequency of responses. Vaccination with comparable doses of Invaplex 50 via the Dolphin TM resulted in higher plasma and ASC immune responses as compared to pipette delivery. Conclusion: In this trial the S. flexneri 2a Invaplex 50 vaccine was safe, well-tolerated and induced robust levels of antigen-specific intestinal IgA and ASC responses. The spray device performed well and offered an advantage over pipette intranasal delivery.Published by Elsevier Ltd.

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