title: A herpes simplex virus 2 (HSV-2) glycoprotein D-expressing nonreplicating dominant-negative HSV-2 virus vaccine is superior to a gD2 subunit vaccine against HSV-2 genital infection in guinea pigs.
abstract: We recently constructed a novel non-replicating dominant-negative HSV-2 recombinant viral vaccine (CJ2-gD2) capable of expressing various HSV-2 antigens that are dominant targets of HSV-2-specific CD8 T-cell response. Importantly, CJ2-gD2 expresses gD2, the HSV-2 major antigen glycoprotein D, as efficiently as wild-type HSV-2 infection and can lead to a nearly 500-fold reduction in wild-type HSV-2 viral replication in cells co-infected with CJ2-gD2 and wild-type HSV-2. In this report, we show that CJ2-gD2 elicits a strong antibody response to various HSV-2 antigens and is highly effective in the prevention of primary and recurrent HSV-2 genital infection and disease in the immunized guinea pigs. The direct comparison study between CJ2-gD2 and a gD2 subunit vaccine (gD2-alum/MPL) with a formulation akin to a vaccine tested in phase III clinical trials shows that CJ2-gD2 is 8 times more effective than the gD2-alum/MPL subunit vaccine in eliciting an anti-HSV-2 specific neutralizing antibody response and offers significantly superior protection against primary and recurrent HSV-2 genital infections. Importantly, no challenge wild-type HSV-2 viral DNA was detectable in dorsal root ganglia DNA isolated from CJ2-gD2-immunized guinea pigs on day 60 post-challenge. CJ2-gD2 should be an excellent HSV-2 vaccine candidate for protection against HSV-2 genital infection and disease in humans.
authors: Department of Surgery, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, United States of America.
authors: Pengwei
authors: P
authors: Zhang
authors: Department of Surgery, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, United States of America.
authors: Lining
authors: L
authors: Xie
authors: Vaccine Research, Merck Research Laboratories, Merck & Co., Inc., West Point, Pennsylvania, United States of America.
authors: John W
authors: JW
authors: Balliet
authors: Vaccine Research, Merck Research Laboratories, Merck & Co., Inc., West Point, Pennsylvania, United States of America.
authors: Danilo R
authors: DR
authors: Casimiro
authors: Department of Surgery, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, United States of America.
authors: Feng
authors: F
authors: Yao
mesh_terms: D000818:Animals; D016466:CHO Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D006168:Guinea Pigs; D006558:Herpes Genitalis / Q000276:immunology / Q000517:prevention & control*; D022301:Herpes Simplex Virus Vaccines / Q000276:immunology*; D006801:Humans; D019444:Vaccines, DNA / Q000276:immunology*; D022223:Vaccines, Subunit / Q000276:immunology; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D022301:Herpes Simplex Virus Vaccines; D019444:Vaccines, DNA; D022223:Vaccines, Subunit; D014759:Viral Envelope Proteins; C040570:glycoprotein D-herpes simplex virus type 2