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Journal of Virology, April 2004, p. 4020-4028, Vol. 78, No. 8
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.8.4020-4028.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Protection from Bacterial Infection by a Single Vaccination with Replication-Deficient Mutant Herpes Simplex Virus Type 1

Henning Lauterbach,1 Kristen M. Kerksiek,1 Dirk H. Busch,2 Elena Berto,3 Aleksandra Bozac,3 Penelope Mavromara,4 Roberto Manservigi,3 Alberto L. Epstein,5 Peggy Marconi,3,{dagger}* and Thomas Brocker1,{dagger}*

Institute for Immunology, Ludwig-Maximilians-University, 80336 Munich,1 Technische Universität Munich, Institute for Medical Microbiology and Hygiene, 81675 Munich, Germany,2 University of Ferrara, Department of Experimental and Diagnostic Medicine, 44100 Ferrara, Italy,3 Molecular Virology Laboratory, Hellenic Pasteur Institute, Athens, Greece,4 University Claude-Bernard Lyon 1, Centre de Genetique Moleculaire et Cellulaire, C.N.R.S., UMR 5534, 69622 Villeurbanne Cedex, France5

Received 26 August 2003/ Accepted 5 November 2003

Adaptive immune responses in which CD8+ T cells recognize pathogen-derived peptides in the context of major histocompatibility complex class I molecules play a major role in the host defense against infection with intracellular pathogens. Cells infected with intracellular bacteria such as Listeria monocytogenes, Salmonella enterica serovar Typhimurium, or Mycobacterium tuberculosis are directly lysed by cytotoxic CD8+ T cells. For this reason, current vaccines for intracellular pathogens, such as subunit vaccines or viable bacterial vaccines, aim to generate robust cytotoxic T-cell responses. In order to investigate the capacity of a herpes simplex virus type 1 (HSV-1) vector to induce strong cytotoxic effector cell responses and protection from infection with intracellular pathogens, we developed a replication-deficient, recombinant HSV-1 (rHSV-1) vaccine. We demonstrate in side-by-side comparison with DNA vaccination that rHSV-1 vaccination induces very strong CD8+ effector T-cell responses. While both vaccines provided protection from infection with L. monocytogenes at low, but lethal doses, only rHSV-1 vaccines could protect from higher infectious doses; HSV-1 induced potent memory cytotoxic T lymphocytes that, upon challenge by pathogens, efficiently protected the animals. Despite the stimulation of relatively low humoral and CD4-T-cell responses, rHSV-1 vectors are strong candidates for future vaccine strategies that confer efficient protection from subsequent infection with intracellular bacteria.

* Corresponding author. Mailing address for T. Brocker: Institute for Immunology, Goethestrasse 31, 80336 Munich, Germany. Phone: 49-89-5996674. Fax: 49-89-5996605. E-mail: tbrocker{at}ifi.med.uni-muenchen.de. Mailing address for P. Marconi: University of Ferrara, Department of Experimental and Diagnostic Medicine, Via Luigi Borsari 46, 44100 Ferrara, Italy. Phone: 390-532-291397. Fax: 390-532-247618. E-mail: mcy{at}dns.unife.it.

{dagger} Shared senior authorship.

Journal of Virology, April 2004, p. 4020-4028, Vol. 78, No. 8
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.8.4020-4028.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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