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Infection and Immunity, January 1999, p. 253-258, Vol. 67, No. 1
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Existing Antilisterial Immunity Does Not Inhibit the Development of a Listeria monocytogenes-Specific Primary Cytotoxic T-Lymphocyte Response

H. G. Archie Bouwer,1,* Hao Shen,2 Xin Fan,2 Jeff F. Miller,3 Ronald A. Barry,1 and David J. Hinrichs1

Immunology Research, Veterans Affairs Medical Center, and Earle A. Chiles Research Institute, Portland, Oregon1; Department of Microbiology and Immunology at University of Pennsylvania Medical School, Philadelphia, Pennsylvania2; and Department of Microbiology and Immunology at UCLA, Los Angeles, California3

Received 28 July 1998/Returned for modification 6 October 1998/Accepted 28 October 1998

Infection of BALB/c mice with Listeria monocytogenes stimulates an antilisterial immune response evident by the appearance of H2-Kd-restricted CD8+ cytotoxic T lymphocytes (CTLs) specific for the nanomer peptides amino acids (aa) 91 to 99 of listeriolysin O (LLO 91-99) and aa 217 to 225 of the p60 molecule (p60 217-225). We have introduced point mutations at anchor residues within LLO 91-99 (92F) or p60 217-225 (218F), and BALB/c mice infected with L. monocytogenes strains containing these point mutations do not develop CTLs specific for LLO 91-99 or p60 217-225, respectively. We have used these strains to test whether primary CTL responses against L. monocytogenes-derived determinants can be stimulated within an environment of existing antilisterial immunity. We found that the development of a primary L. monocytogenes-specific CTL response is not altered by existing immunity to L. monocytogenes. For example, primary immunization with the p60 218F strain of L. monocytogenes followed by a secondary immunization with wild-type L. monocytogenes results in stimulation of p60 217-225-specific CTLs at primary response levels and LLO 91-99-specific effectors at levels consistent with a memory CTL response. Similarly, primary immunization with the 92F strain of L. monocytogenes followed by a secondary immunization with wild-type L. monocytogenes results in stimulation of LLO 91-99-specific CTLs at primary response levels and p60 217-225-specific effectors at levels consistent with a memory CTL response. These results provide additional support for the use of L. monocytogenes as a recombinant vaccine vector and show that antivector immunity does not inhibit the development of a primary CTL response when the epitope is delivered by L. monocytogenes as the vaccine strain.

* Corresponding author. Mailing address: Immunology Research RD21, VAMC, Portland, OR 97201. Phone: (503) 721-7840. Fax: (503) 273-5135. E-mail: bouwera{at}ohsu.edu.

Infection and Immunity, January 1999, p. 253-258, Vol. 67, No. 1
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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