TITLE

Herpes Simplex Virus 2 (HSV-2) Infected Cell Proteins Are among the Most Dominant Antigens of a Live-Attenuated HSV-2 Vaccine

AUTHOR(S)
Geltz, Joshua J.; Gershburg, Edward; Halford, William P.
PUB. DATE
February 2015
SOURCE
PLoS ONE;Feb2015, Vol. 10 Issue 2, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Virion glycoproteins such as glycoprotein D (gD) are believed to be the dominant antigens of herpes simplex virus 2 (HSV-2). We have observed that mice immunized with a live HSV-2 ICP0- mutant virus, HSV-2 0ΔNLS, are 10 to 100 times better protected against genital herpes than mice immunized with a HSV-2 gD subunit vaccine (PLoS ONE 6:e17748). In light of these results, we sought to determine which viral proteins were the dominant antibody-generators (antigens) of the live HSV-2 0ΔNLS vaccine. Western blot analyses indicated the live HSV-2 0ΔNLS vaccine elicited an IgG antibody response against 9 or more viral proteins. Many antibodies were directed against infected-cell proteins of >100 kDa in size, and only 10 ± 5% of antibodies were directed against gD. Immunoprecipitation (IP) of total HSV-2 antigen with 0ΔNLS antiserum pulled down 19 viral proteins. Mass spectrometry suggested 44% of immunoprecipitated viral peptides were derived from two HSV-2 infected cells proteins, RR-1 and ICP8, whereas only 14% of immunoprecipitated peptides were derived from HSV-2’s thirteen glycoproteins. Collectively, the results suggest the immune response to the live HSV-2 0ΔNLS vaccine includes antibodies specific for infected cell proteins, capsid proteins, tegument proteins, and glycoproteins. This increased breadth of antibody-generating proteins may contribute to the live HSV-2 vaccine’s capacity to elicit superior protection against genital herpes relative to a gD subunit vaccine.
ACCESSION #
101319675

 

Related Articles

  • Binding of HSV-1 Glycoprotein K (gK) to Signal Peptide Peptidase (SPP) Is Required for Virus Infectivity. Allen, Sariah J.; Mott, Kevin R.; Matsuura, Yoshiharu; Moriishi, Kohji; Kousoulas, Konstantin G.; Ghiasi, Homayon // PLoS ONE;Jan2014, Vol. 9 Issue 1, p1 

    Glycoprotein K (gK) is a virion envelope protein of herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), which plays important roles in virion entry, morphogenesis and egress. Two-hybrid and pull-down assays were utilized to demonstrate that gK and no other HSV-1 genes specifically binds to...

  • Characterisation of the epitope for a herpes simplex virus glycoprotein B-specific monoclonal antibody with high protective capacity. Däumer, Martin P.; Schneider, Beate; Giesen, Doris M.; Aziz, Sheriff; Kaiser, Rolf; Kupfer, Bernd; Schneweis, Karl E.; Schneider-Mergener, Jens; Reineke, Ulrich; Matz, Bertfried; Eis-Hübinger, Anna M. // Medical Microbiology & Immunology;May2011, Vol. 200 Issue 2, p85 

    Monoclonal antibody (MAb) 2c, specific for glycoprotein B of herpes simplex virus (HSV), had been shown to mediate clearance of infection from the mucous membranes of mice, thereby completely inhibiting mucocutaneous inflammation and lethality, even in mice depleted of both CD4 and CD8 cells....

  • Immunization with a Dominant-Negative Recombinant HSV Type 1 Protects against HSV-1 Skin Disease in Guinea Pigs. Brans, Richard; Eriksson, Elof; Yao, Feng // Journal of Investigative Dermatology;Dec2008, Vol. 128 Issue 12, p2825 

    CJ9-gD belongs to a new class of replication-defective recombinant herpes simplex viruses (HSVs) type 1 that can function in trans to prevent the replication of wild-type HSV in co-infected cells. Furthermore, CJ9-gD cannot establish latent infection in vivo and it expresses high levels of the...

  • 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...

  • Cross-presentation and genome-wide screening reveal candidate T cells antigens for a herpes simplex virus type 1 vaccine. Lichen Jing; Haas, Jürgen; Chong, Tiana M.; Bruckner, Joseph J.; Dann, Greg C.; Lichun Dong; Marshak, Joshua O.; McClurkan, Christopher L.; Yamamoto, Tori N.; Bailer, Susanne M.; Laing, Kerry J.; Wald, Anna; Verjans, Georges M. G. M.; Koelle, David M. // Journal of Clinical Investigation;Feb2012, Vol. 122 Issue 2, p654 

    Herpes simplex virus type 1 (HSV-1) not only causes painful recurrent oral-labial infections, it can also cause permanent brain damage and blindness. There is currently no HSV-1 vaccine. An effective vaccine must stimulate coordinated T cell responses, but the large size of the genome and the...

  • Binding of Herpes Simplex Virus Type-1 Virions Leads to the Induction of Intracellular Signalling in the Absence of Virus Entry. MacLeod, Iain J.; Minson, Tony // PLoS ONE;2010, Vol. 5 Issue 3, p1 

    The envelope of HSV-1 contains a number of glycoproteins, four of which are essential for virus entry. Virus particles lacking gB, gD, gH or gL are entry-defective, although these viruses retain the ability to bind to the plasma membrane via the remaining glycoproteins. Soluble forms of gD have...

  • 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."

  • 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."

  • Characterization of T-cell reactive epitopes in glycoprotein G of herpes simplex virus type 2 using synthetic peptides. Bellner, L.; L�whagen, G.-B.; Tunb�ck, P.; Nordstr�m, I.; Liljeqvist, J.-�.; Eriksson, K. // Archives of Virology;Jul2005, Vol. 150 Issue 7, p1393 

    We have previously shown that the CD4+ T-cell response to herpes simplex virus type 2 glycoprotein G-2 is type-specific and can thus be used to evaluate herpes simplex virus type 2-specific T-cell responses in individuals with a concomitant herpes simplex virus type 1 infection. In this study we...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

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

Try another library?
Sign out of this library

Other Topics