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Clinical and Vaccine Immunology, April 2009, p. 574-586, Vol. 16, No. 4
1071-412X/09/$08.00+0     doi:10.1128/CVI.00435-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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

Robert W. Kaminski,1* K. Ross Turbyfill,1 C. Chao,2 W. M. Ching,2 and Edwin V. Oaks1

Division of Bacterial and Rickettsial Diseases, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910-7500,1 Rickettsial Diseases Research Program, Naval Medical Research Center, Silver Spring, Maryland 20910-75002

Received 21 November 2008/ Returned for modification 7 January 2009/ Accepted 8 February 2009

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.

* Corresponding author. Mailing address: Division of Bacterial and Rickettsial Diseases, Walter Reed Army Institute of Research, 503 Robert Grant Ave., Silver Spring, MD 20910. Phone: (301) 319-9803. Fax: (301) 319-9801. E-mail: Robert.Kaminski{at}amedd.army.mil

{triangledown} Published ahead of print on 18 February 2009.

Clinical and Vaccine Immunology, April 2009, p. 574-586, Vol. 16, No. 4
1071-412X/09/$08.00+0     doi:10.1128/CVI.00435-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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