Immunization with a dominant-negative recombinant HSV type 1 protects against HSV-1 skin disease in guinea pigs.
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.
Brans
Richard
R
Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA.
Eriksson
Elof
E
Yao
Feng
F
D000818:Animals; D000914:Antibodies, Viral / Q000737:chemistry; D005260:Female; D005727:Ganglia, Spinal / Q000821:virology; D005799:Genes, Dominant; D006168:Guinea Pigs; D006561:Herpes Simplex / Q000276:immunology / Q000517:prevention & control* / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000378:metabolism*; D022283:Herpesvirus Vaccines / Q000627:therapeutic use*; D007114:Immunization; D007074:Immunoglobulin G / Q000737:chemistry; D016133:Polymerase Chain Reaction; D012867:Skin / Q000821:virology*; D012871:Skin Diseases / Q000517:prevention & control* / Q000821:virology*; D014759:Viral Envelope Proteins / Q000378:metabolism
D000914:Antibodies, Viral; D022283:Herpesvirus Vaccines; D007074:Immunoglobulin G; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1