Original Article

Subject Category: Immunology/Infection

Journal of Investigative Dermatology advance online publication 22 May 2008; doi: 10.1038/jid.2008.142

Immunization with a Dominant-Negative Recombinant HSV Type 1 Protects against HSV-1 Skin Disease in Guinea Pigs

The study was carried out in Boston, MA, USA.

Richard Brans1, Elof Eriksson1 and Feng Yao1

1Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA

Correspondence: Dr Feng Yao, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA. E-mail: fyao@rics.bwh.harvard.edu

Received 24 September 2007; Revised 27 March 2008; Accepted 31 March 2008; Published online 22 May 2008.

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Abstract

CJ9-gD belongs to a new class of replication-defective recombinant herpes simplex viruses (HSVs) type 1 that can function in trans to prevent the replication of wild-type HSV in co-infected cells. Furthermore, CJ9-gD cannot establish latent infection in vivo and it expresses high levels of the major HSV-1 antigen glycoprotein D immediately following infection. In this study we show that guinea pigs immunized with CJ9-gD developed at least 9,600-fold higher titers of HSV-1-specific neutralization antibodies than mock-immunized controls. After challenge with wild-type HSV-1, all 10 mock-immunized guinea pigs developed multiple skin lesions with an average of 53.3 lesions per animal, whereas only 2 minor lesions were found in 1 of 10 CJ9-gD-immunized animals, representing a 267-fold reduction on the incidence of primary herpetic skin lesions in immunized animals. Quantitative PCR analysis revealed that the amount and frequency of wild-type HSV-1 viral DNA present in dorsal root ganglia of immunized animals was significantly lower than that in mock-immunized controls. Collectively, we demonstrate that vaccination with CJ9-gD elicits strong and protective immune responses against primary HSV-1 skin disease and reduces the extent of latent infection by challenge virus.

Abbreviations:

gD, glycoprotein D; HSV, herpes simplex virus

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