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A 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 Mosley, R.

PloS one, 2011-03, Vol.6 (3), p.e17748 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
A live-attenuated HSV-2 ICP0 virus elicits 10 to 100 times greater protection against genital herpes than a glycoprotein D subunit vaccine
Autor: Halford, William P ; Püschel, Ringo ; Gershburg, Edward ; Wilber, Andrew ; Gershburg, Svetlana ; Rakowski, Brandon
Mosley, R.
Assuntos: Alum ; Aluminum sulfate ; Animals ; Antibody Formation - immunology ; Antigens ; Attenuation ; Biology ; Chicken pox ; Clinical trials ; Female ; Gene expression ; Genomes ; Glycoprotein D ; Glycoproteins ; Green Fluorescent Proteins - metabolism ; Herpes Genitalis - immunology ; Herpes Genitalis - prevention & control ; Herpes Genitalis - virology ; Herpes simplex ; Herpes simplex virus 2 ; Herpes Simplex Virus Vaccines - immunology ; Herpes viruses ; Herpesvirus 2, Human - immunology ; Herpesvirus 2, Human - pathogenicity ; Imaging, Three-Dimensional ; Immunity - immunology ; Immunization ; Immunoglobulin G - immunology ; Immunology ; Lipid A ; Luciferases - metabolism ; Medical research ; Medicine ; Mice ; Mice, Inbred ICR ; Monophosphoryl lipid A ; Muridae ; Nuclear Localization Signals ; Pharmaceutical industry ; Polypeptides ; Proteins ; Sequence Deletion ; Studies ; Vaccines ; Vaccines, Attenuated ; Vaccines, Subunit - immunology ; Vagina ; Vagina - virology ; Viral Envelope Proteins - immunology ; Viral Proteins - immunology ; Virulence - immunology ; Viruses
É parte de: PloS one, 2011-03, Vol.6 (3), p.e17748
Notas: ObjectType-Article-2
SourceType-Scholarly Journals-1
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Conceived and designed the experiments: WPH BR RP. Performed the experiments: WPH BR RP SG EG AW. Analyzed the data: WPH EG AW. Contributed reagents/materials/analysis tools: WPH BR RP SG EG AW. Wrote the manuscript: WPH.
Descrição: 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 wild-type 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 0ΔNLS-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.
Editor: United States: Public Library of Science
Idioma: Inglês

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A 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 Mosley, R.

United States: Public Library of Science

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