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Infection and Immunity, May 2004, p. 2810-2816, Vol. 72, No. 5
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.5.2810-2816.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Flagellin Fusion Proteins as Adjuvants or Vaccines Induce Specific Immune Responses

Camilo Cuadros, Francisco J. Lopez-Hernandez, Ana Lucia Dominguez, Michael McClelland, and Joseph Lustgarten*

Sidney Kimmel Cancer Center, San Diego, California

Received 4 December 2003/ Returned for modification 14 January 2004/ Accepted 26 January 2004

Vaccination is the most efficient prophylaxis against a variety of infectious diseases. New vaccination strategies rely on the incorporation of effective adjuvants, which stimulate the innate immune response and, in turn, activate the adaptive immune response. It is well established that flagellin induces inflammatory responses through the activation of antigen-presenting cells (APCs). In order to evaluate whether flagellin can serve as a carrier for the development of adjuvants or vaccines, we prepared a flagellin-enhanced green fluorescent protein (EGFP) fusion protein. Our results demonstrate that a flagellin-EGFP fusion protein is capable of stimulating APCs, resulting in the maturation of these cells and secretion of proinflammatory cytokines. Furthermore, APCs pulsed with the flagellin-EGFP fusion protein effectively process and present EGFP antigens. More importantly, animals immunized with the flagellin-EGFP fusion protein developed specific anti-EGFP T-cell responses. In contrast, recombinant EGFP was not able to stimulate APCs, nor did it induce a T-cell response. Thus, recombinant-flagellin fusion proteins may be suitable carriers as adjuvants or vaccines for the development of new vaccination strategies to induce and boost immune responses against infectious diseases and cancer.

* Corresponding author. Mailing address: Joseph Lustgarten, Sidney Kimmel Cancer Center, 10835 Altman Row, San Diego, CA 92121. Phone: (858) 410-4190. Fax: (858) 450-3251. E-mail: jlustgarten{at}skcc.org.

Editor: D. L. Burns

Infection and Immunity, May 2004, p. 2810-2816, Vol. 72, No. 5
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.5.2810-2816.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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