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Vaccine. 2006 Mar 6;24(10):1644-52. Epub 2005 Oct 5.

Genetically engineered herpes simplex viruses that express IL-12 or GM-CSF as vaccine candidates.

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Department of Pediatrics, Division of Infectious Diseases, The University of Alabama at Birmingham, CHB 118B, 1600 6th Avenue South, Birmingham, AL 35233, USA.


We are using genetically modified, conditionally replicating herpes simplex virus (HSV) that express either interleukin (IL)-12 or granulocyte macrophage-colony stimulating factor (GM-CSF) as live, attenuated vaccine candidates for protection against HSV infection and/or disease. We report the following: (1) animals previously vaccinated with these candidate vaccines exhibited dose-dependent protection after intranasal, intraperitoneal or intracranial challenge with the highly virulent E377-MB wild-type HSV-1; (2) the IL-12 expressing virus (M002) consistently conferred protection at lower immunization doses than GM-CSF expressing virus (M004); (3) between 80 and 100% protection from E377-MB challenge was conferred after intramuscular immunization of mice with any of the three Deltagamma1 34.5 HSV, as opposed to 50% protection elicited after immunization with wild-type HSV-1 (F); and (4) latent virus was not detected at a higher rate in animals immunized and subsequently challenged with E377-MB than in immunized animals alone. These data suggest that conditionally replicating, cytokine-expressing HSV are able to elicit protective immune responses while retaining safety in an experimental murine model.

[Indexed for MEDLINE]

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