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Infection and Immunity, July 1999, p. 3290-3296, Vol. 67, No. 7
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Cytotoxic T-Lymphocyte Epitopes Fused to Anthrax Toxin Induce Protective Antiviral Immunity

Amy M. Doling,1 Jimmy D. Ballard,1,dagger Hao Shen,2,Dagger Kaja Murali Krishna,2 Rafi Ahmed,2 R. John Collier,1 and Michael N. Starnbach1,*

Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115,1 and Emory Vaccine Center and Department of Microbiology and Immunology, Emory University, Atlanta, Georgia 303222

Received 23 December 1998/Returned for modification 17 March 1999/Accepted 8 April 1999

We have investigated the use of the protective antigen (PA) and lethal factor (LF) components of anthrax toxin as a system for in vivo delivery of cytotoxic T-lymphocyte (CTL) epitopes. During intoxication, PA directs the translocation of LF into the cytoplasm of mammalian cells. Here we demonstrate that antiviral immunity can be induced in BALB/c mice immunized with PA plus a fusion protein containing the N-terminal 255 amino acids of LF (LFn) and an epitope from the nucleoprotein (NP) of lymphocytic choriomeningitis virus. We also demonstrate that BALB/c mice immunized with a single LFn fusion protein containing NP and listeriolysin O protein epitopes in tandem mount a CTL response against both pathogens. Furthermore, we show that NP-specific CTL are primed in both BALB/c and C57BL/6 mice when the mice are immunized with a single fusion containing two epitopes, one presented by Ld and one presented by Db. The data presented here demonstrate the versatility of the anthrax toxin delivery system and indicate that this system may be used as a general approach to vaccinate outbred populations against a variety of pathogens.

* Corresponding author. Mailing address: Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Ave., Boston, MA 02115. Phone: (617) 432-1873. Fax: (617) 738-7664. E-mail: starnbach{at}hms.harvard.edu.

dagger Present address: The University of Oklahoma, Department of Botany and Microbiology, Norman, OK 73019.

Dagger Present address: University of Pennsylvania School of Medicine, Department of Microbiology, Philadelphia, PA 19104-6076.

Infection and Immunity, July 1999, p. 3290-3296, Vol. 67, No. 7
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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