Immunization with a dominant-negative recombinant Herpes Simplex Virus (HSV) type 1 protects against HSV-2 genital disease in guinea pigs.
BACKGROUND
CJ9-gD is a novel dominant-negative recombinant herpes simplex virus type 1 (HSV-1) that is completely replication-defective, cannot establish detectable latent infection in vivo, and expresses high levels of the major HSV-1 antigen glycoprotein D immediately following infection. In the present study, CJ9-gD was evaluated as a vaccine against HSV-2 genital infection in guinea pigs.


RESULTS
Animals immunized with CJ9-gD developed at least 700-fold higher titers of HSV-2-specific neutralization antibodies than mock-immunized controls. After challenge with wild-type HSV-2, all 10 control guinea pigs developed multiple genital lesions with an average of 21 lesions per animal. In contrast, only 2 minor lesions were found in 2 of 8 CJ9-gD-immunized animals, representing a 40-fold reduction on the incidence of primary genital lesions in immunized animals (p < 0.0001). Immunization significantly reduced the amount and duration of viral shedding and provided complete protection against neurological symptoms, while 90% of mock-immunized animals succumbed due to the severity of disease. Importantly, immunized animals showed no signs of recurrent disease or viral shedding during a 60-days observation period after recovery from primary infection, and carried 50-fold less latent viral DNA load in their dorsal root ganglia than the surviving mock-vaccinated controls (p < 0.0001).


CONCLUSIONS
Collectively, we demonstrate that vaccination with the HSV-1 recombinant CJ9-gD elicits strong and protective immune responses against primary and recurrent HSV-2 genital disease and significantly reduces the extent of latent infection.
Department of Surgery, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA.
Richard
R
Brans
Feng
F
Yao
D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D006168:Guinea Pigs; D006558:Herpes Genitalis / Q000473:pathology / Q000517:prevention & control*; D022301:Herpes Simplex Virus Vaccines / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D009422:Nervous System Diseases / Q000517:prevention & control; D017201:Virus Shedding
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D022301:Herpes Simplex Virus Vaccines