ME-609: A Treatment for Recurrent Herpes Simplex Virus Infections

Author:

Harmenberg Johan G12,Awan Aftab R3,Alenius Stefan4,Ståhle Lars5,Erlandsson Anna C6,Lekare Gunilla7,Flink Ola8,Augustsson Elisabeth1,Larsson Torbjörn1,Wikström Ann-Charlotte6,Stierna Pontus9,Field Hugh J3,Larsson Alf G8,Öberg Bo12

Affiliation:

1. Medivir AB, Huddinge, Sweden

2. Karolinska Institutet, Stockholm, Sweden

3. Centre for Veterinary Science, University of Cambridge, Cambridge, UK

4. National Veterinary Institute, Uppsala, Sweden

5. Department of Clinical Pharmacology, Karolinska Institutet, Huddinge University Hospital, Huddinge, Sweden

6. Department of Medical Nutrition, Karolinska Institutet, Huddinge, Sweden

7. CCS AB, Borlänge, Sweden

8. AstraZeneca, Södertälje, Sweden

9. Department of Clinical Science, Huddinge University Hospital, Huddinge, Sweden

Abstract

Studies in conventional murine models of HSV infection use immunologically naive animals. These models thus mimic primary infections rather than recurrent infections in humans. We have, therefore, used a newly developed mouse model that more closely mimics recurrent HSV infection in humans. In this model, the mice are infected, and zosteriform HSV-1 infection develops in the presence of a primed immune response using adoptive transfer of immunity (ATI) as we have described previously. Using the ATI mouse model, it has been shown that a more beneficial therapy for recurrent mucocutaneous HSV infection could be achieved by controlling both the viral replication and the inflammatory response to the virus. Topical treatment was initiated in this model at the time of first occurrence of symptoms and was given three times daily for 4 days. Topical treatment with ME-609 (which contains 5% acyclovir and 1% hydrocortisone) in the ATI mouse model was substantially more efficacious than 5% Zovirax® cream, 1% hydrocortisone or no treatment, respectively. The beneficial properties of ME-609 were also found to be superior to those of Zovirax cream when tested in the standard guinea pig model, representing a primary HSV infection. ME-609 represents a novel treatment principle of recurrent HSV infections and the present paper summarizes the preclinical and early clinical experience of ME-609.

Publisher

SAGE Publications

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