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
March 2011
PLoS ONE;2011, Vol. 6 Issue 3, p1
Academic Journal
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 date, gD-2 vaccines have yielded equivocal protection in clinical trials. Therefore, using a small animal model, we sought to determine if a live-attenuated HSV-2 ICP0- virus would elicit better protection against genital herpes than a gD-2 subunit vaccine. Mice immunized with gD-2 and a potent adjuvant (alum+monophosphoryl lipid A) produced high titers of gD-2 antibody. While gD-2-immunized mice possessed significant resistance to HSV-2, only 3 of 45 gD-2-immunized mice survived an overwhelming challenge of the vagina or eyes with wildtype HSV-2 (MS strain). In contrast, 114 of 115 mice immunized with a live HSV-2 ICP0- virus, 0ΔNLS, survived the same HSV- 2 MS challenges. Likewise, 0ΔNLS-immunized mice shed an average 125-fold less HSV-2 MS challenge virus per vagina relative to gD-2-immunized mice. In vivo imaging demonstrated that a luciferase-expressing HSV-2 challenge virus failed to establish a detectable infection in 0DNLS-immunized mice, whereas the same virus readily infected naïve and gD-2- immunized mice. Collectively, these results suggest that a HSV-2 vaccine might be more likely to prevent genital herpes if it contained a live-attenuated HSV-2 virus rather than a single HSV-2 protein.


Related Articles

  • 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."

  • 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."

  • 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...

  • 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...

  • Early Events in Herpes Simplex Virus Lifecycle with Implications for an Infection of Lifetime. Salameh, Sarah; Sheth, Urmi; Shukla, Deepak // Open Virology Journal;2012, Vol. 6, p1 

    Affecting a large percentage of human population herpes simplex virus (HSV) types -1 and -2 mainly cause oral, ocular, and genital diseases. Infection begins with viral entry into a host cell, which may be preceded by viral "surfing" along filopodia. Viral glycoproteins then bind to one or more...

  • Better Neutralization of Herpes Simplex Virus Type 1 (HSV-1) Than HSV-2 by Antibody From Recipients of GlaxoSmithKline HSV-2 Glycoprotein D2 Subunit Vaccine. Awasthi, Sita; Belshe, Robert B.; Friedman, Harvey M. // Journal of Infectious Diseases;Aug2014, Vol. 210 Issue 4, p571 

    The Herpevac Trial evaluated a herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) subunit vaccine to prevent genital herpes. Unexpectedly, the vaccine protected against genital HSV-1 infection but not genital HSV-2 infection. We evaluated sera from 30 women seronegative for HSV-1 and HSV-2...

  • Rising incidence and prevalence of herpes simplex type 2 infection in a cohort of 26 year old New Zealanders. Eberhart-Phillips, Jason E; Dickson, Nigel P; Paul, Charlotte; Herbison, G Peter; Taylor, Janette; Cunningham, Anthony L // Sexually Transmitted Infections;Oct2001, Vol. 77 Issue 5, p353 

    Objectives: To examine changes in the incidence and prevalence of herpes simplex type 2 (HSV-2) infection in a birth cohort of 26 year old New Zealanders in whom seroprevalence had been measured at 3.4% at age 21. Methods: Sen from 869 cohort members were tested using an indirect IgG enzyme...

  • Antibody to herpes simplex virus type 2 as serological marker of sexual lifestyle in populations. Cowan, Frances M.; Johnson, Anne M.; Ashley, Rhoda; Corey, Lawrence; Mindel, Adrian // BMJ: British Medical Journal (International Edition);11/19/94, Vol. 309 Issue 6965, p1325 

    Assesses the suitability of herpes simplex virus types 2 as a serological marker of sexual behavior in London population in England. Epidemiology of antibody to herpes simplex virus type 2; Association of antibody with sexual orientation and years of sexual activity of population; Prevalence of...

  • A Novel DNA Vaccine Technology Conveying Protection against a Lethal Herpes Simplex Viral Challenge in Mice. Dutton, Julie L.; Li, Bo; Woo, Wai-Ping; Marshak, Joshua O.; Xu, Yan; Huang, Meei-li; Dong, Lichun; Frazer, Ian H.; Koelle, David M. // PLoS ONE;Oct2013, Vol. 8 Issue 10, p1 

    While there are a number of licensed veterinary DNA vaccines, to date, none have been licensed for use in humans. Here, we demonstrate that a novel technology designed to enhance the immunogenicity of DNA vaccines protects against lethal herpes simplex virus 2 (HSV-2) challenge in a murine...


Read the Article


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

Try another library?
Sign out of this library

Other Topics