High-Level Expression of Glycoprotein D by a Dominant-Negative HSV-1 Virus Augments its Efficacy as a Vaccine against HSV-1 Infection

Lu, Zheming; Brans, Richard; Akhrameyeva, Natali V; Murakami, Nao; Xu, Ximing; Yao, Feng
May 2009
Journal of Investigative Dermatology;May2009, Vol. 129 Issue 5, p1174
Academic Journal
Using the T-REx (Invitrogen, Carlsbad, CA) gene switch technology, we previously generated a dominant-negative herpes simplex virus (HSV)-1 recombinant, CJ83193, capable of inhibiting its own replication as well as that of wild-type HSV-1 and HSV-2. It has been further demonstrated that CJ83193 is an effective vaccine against HSV-1 infection in a mouse ocular model. To ensure its safety and augment its efficacy, we generated an improved CJ83193-like HSV-1 recombinant, CJ9-gD, which contains a deletion in an HSV-1 essential gene and encodes an extra copy of gene-encoding glycoprotein D (gD) driven by the tetO-bearing human cytomegalovirus major immediate-early promoter. Unlike CJ83193, which exhibits limited plaque-forming capability in Vero cells and expresses little gD in infected cells, CJ9-gD is completely replication defective, yields high-level expression of gD following infection, and cannot establish detectable infection in mouse trigeminal ganglia following intranasal and ocular inoculation. Mice immunized with CJ9-gD produced 3.5-fold higher HSV-1 neutralizing antibody titer than CJ83193-immunized mice, and were completely protected from herpetic ocular disease following corneal challenge with wild-type HSV-1. Moreover, immunization of mice with CJ9-gD elicited a strong HSV-1-specific T-cell response and led to an 80% reduction in latent infection by challenge wild-type HSV-1 compared with the mock-immunized control.Journal of Investigative Dermatology (2009) 129, 1174–1184; doi:10.1038/jid.2008.349; published online 13 November 2008


Related Articles

  • Virology: Back to the HSV drawing board. Molloy, Sheilagh // Nature Reviews Microbiology;Feb2012, Vol. 10 Issue 2, p82 

    The article discusses the glycoprotein D (Gd)-based vaccine field trial against the herpes simplex virus type 2 (HSV-2) which references the study "Efficacy results of a trial of a herpes simplex vaccine," by R. B. Belshe and colleagues in the 2012 issue of "New England Journal of Medicine."

  • Live-Attenuated HSV-2 ICP0- Virus Elicits 10 to 100 Times Greater Protection against Genital Herpes than a Glycoprotein D Subunit Vaccine. Halford, William P.; Püschel, Ringo; Gershburg, Edward; Wilber, Andrew; Gershburg, Svetlana; Rakowski, Brandon // PLoS ONE;2011, Vol. 6 Issue 3, p1 

    Glycoprotein D (gD-2) is the entry receptor of herpes simplex virus 2 (HSV-2), and is the immunogen in the pharmaceutical industry's lead HSV-2 vaccine candidate. Efforts to prevent genital herpes using gD-2 subunit vaccines have been ongoing for 20 years at a cost in excess of $100 million. To...

  • Vaccine antibodies correlated with protection against HSV-1. Shafer, Emily // Infectious Disease News;Jan2014, Vol. 27 Issue 1, p21 

    The article reports that antibodies to herpes simplex virus type 2 glycoprotein D correlated with protection against herpes simplex virus type 1, according to research by Robert Belshe and colleagues that was published in the 2013 issue of "The Journal of Infectious Diseases."

  • Efficacy Results of a Trial of a Herpes Simplex Vaccine. Belshe, Robert B.; Leone, Peter A.; Bernstein, David I.; Wald, Anna; Levin, Myron J.; Stapleton, Jack T.; Gorfinkel, Iris; Morrow, Rhoda L. Ashley; Ewell, Marian G.; Stokes-Riner, Abbie; Dubin, Gary; Heineman, Thomas C.; Schulte, Joann M.; Deal, Carolyn D. // New England Journal of Medicine;1/5/2012, Vol. 366 Issue 1, p34 

    Background: Two previous studies of a herpes simplex virus type 2 (HSV-2) subunit vaccine containing glycoprotein D in HSV-discordant couples revealed 73% and 74% efficacy against genital disease in women who were negative for both HSV type 1 (HSV-1) and HSV-2 antibodies. Efficacy was not...

  • Safety and Immunogenicity of Glycoprotein D-- Adjuvant Genital Herpes Vaccine. Bernstein, David I.; Aoki, Fred Y.; Tyring, Stephen K.; Stanberry, Lawrence R.; St-Pierre, Claude; Shafran, Stephen D.; Leroux-Roels, Geert; Van Herck, Koen; Bollaerts, Anne; Dubin, Gary // Clinical Infectious Diseases;5/1/2005, Vol. 40 Issue 9, p1271 

    Background. Two previous trials have suggested that a herpes simplex virus (HSV) type 2 glycoprotein D (gD) vaccine combined with the adjuvants alum and 3'-O-deacylated-monophosphoryl lipid A (MPL) is well tolerated and provides protection against genital herpes disease in women with no...

  • Single dose of Glycoprotein K (gK)-deleted HSV-1 live-attenuated virus protects mice against lethal vaginal challenge with HSV-1 and HSV-2 and induces lasting T cell memory immune responses. Iyer, Arun V.; Pahar, Bapi; Chouljenko, Vladimir N.; Walker, Jason D.; Stanfield, Brent; Kousoulas, Konstantin G. // Virology Journal;2013, Vol. 10 Issue 1, p2 

    Background Herpes simplex virus type-1(HSV-1) and HSV-2 are important human pathogens that cause significant ocular and urogenital complications, respectively. We have previously shown that HSV-1 virions lacking glycoprotein K (gK) are unable to enter into neurons via synaptic axonal membranes...

  • Intravascular naked DNA vaccine encoding glycoprotein B induces protective humoral and cellular immunity against herpes simplex virus type 1 infection in mice. Cui, F-D.; Asada, H.; Kishida, T.; Itokawa, Y.; Nakaya, T.; Ueda, Y.; Yamagishi, H.; Gojo, S.; Kita, M.; Imanishi, J.; Mazda, O. // Gene Therapy;Dec2003, Vol. 10 Issue 25, p2059 

    Naked plasmid DNA (pDNA) vaccine expressing herpes simplex virus type 1 (HSV-1) glycoprotein B (gB) was tested for protective activity against acute HSV-1 infection in mice. The pDNA was intravenously injected into Balb/c mice via their tail vein under high pressure, and the vaccination was...

  • The efficacy of a DNA vaccine encoding herpes simplex virus type 1 (HSV-1) glycoprotein D in decreasing ocular disease severity following corneal HSV-1 challenge. Frye, T. D.; Chiou, H. C.; Hull, B. E.; Bigley, N. J. // Archives of Virology;Sep2002, Vol. 147 Issue 9, p1747 

    Summary. Antiviral effects of a DNA vaccine against herpes simplex virus 1 (HSV-1) glycoprotein D (gD) were evaluated in eight week-old female BALB/c mice. The nuclease-insensitive construct (gD-ASOR) consisted of an HSV-1 gD encoding plasmid coupled to asialo orosomucoid (ASOR), targeting it to...

  • Prediction and Identification of Potential Immunodominant Epitopes in Glycoproteins B, C, E, G, and I of Herpes Simplex Virus Type 2. Mingjie Pan; Xingsheng Wang; Jianmin Liao; Dengke Yin; Suqin Li; Ying Pan; Yao Wang; Guangyan Xie; Shumin Zhang; Yuexi Li // Clinical & Developmental Immunology;2012, p1 

    Twenty B candidate epitopes of glycoproteins B (gB2), C (gC2), E (gE2), G (gG2), and I (gI2) of herpes simplex virus type 2 (HSV-2) were predicted using DNAstar, Biosun, and Antheprot methods combined with the polynomial method. Subsequently, the biological functions of the peptides were tested...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics