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: Pengwei Zhang, Lining Xie, John W Balliet, Danilo R Casimiro, Feng Yao
• Journal: PloS one (PLoS One) Vol. 9 Issue 6 Pg. e101373 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24979708 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Herpes Simplex Virus Vaccines
• Vaccines, DNA
• Vaccines, Subunit
• Viral Envelope Proteins
• glycoprotein D-herpes simplex virus type 2

Topics

• Animals
• CHO Cells
• Cell Line, Tumor
• Chlorocebus aethiops
• Cricetinae
• Cricetulus
• Female
• Guinea Pigs
• Herpes Genitalis (immunology, prevention & control)
• Herpes Simplex Virus Vaccines (immunology)
• Humans
• Vaccines, DNA (immunology)
• Vaccines, Subunit (immunology)
• Vero Cells
• Viral Envelope Proteins (immunology)