Herpes simplex type 2 virus deleted in glycoprotein D protects against vaginal, skin and neural disease

ELife
Christopher PetroWilliam R Jacobs

Abstract

Subunit vaccines comprised of glycoprotein D (gD-2) failed to prevent HSV-2 highlighting need for novel strategies. To test the hypothesis that deletion of gD-2 unmasks protective antigens, we evaluated the efficacy and safety of an HSV-2 virus deleted in gD-2 and complemented allowing a single round of replication on cells expressing HSV-1 gD (ΔgD(-/+gD-1)). Subcutaneous immunization of C57BL/6 or BALB/c mice with ΔgD(-/+gD1) provided 100% protection against lethal intravaginal or skin challenges and prevented latency. ΔgD(-/+gD1) elicited no disease in SCID mice, whereas 1000-fold lower doses of wild-type virus were lethal. HSV-specific antibodies were detected in serum (titer 1:800,000) following immunization and in vaginal washes after intravaginal challenge. The antibodies elicited cell-mediated cytotoxicity, but little neutralizing activity. Passive transfer of immune serum completely protected wild-type, but not Fcγ-receptor or neonatal Fc-receptor knock-out mice. These studies demonstrate that non-neutralizing Fc-mediated humoral responses confer protection and support advancement of this attenuated vaccine.

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Citations

Aug 19, 2015·Brain : a Journal of Neurology·Heiko Braak, Kelly Del Tredici
Apr 27, 2016·Current Clinical Microbiology Reports·Brent Stanfield, Konstantin Gus Kousoulas
Mar 11, 2015·ELife·Silvia Bolland, Susan K Pierce
May 20, 2016·Medical Microbiology and Immunology·Eugenia Corrales-AguilarHartmut Hengel
Aug 19, 2016·JCI Insight·Christopher D PetroBetsy C Herold
Jul 27, 2017·Mucosal Immunology·A VareseA Ceballos
Mar 27, 2018·Glycobiology·Ieva Bagdonaite, Hans H Wandall
Aug 2, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Derek J RoyerDaniel J J Carr
Nov 28, 2017·Frontiers in Immunology·Angello Retamal-DíazPablo A González
Dec 19, 2018·Current Clinical Microbiology Reports·Paul J F RiderKonstantin G Kousoulas
Mar 4, 2020·The Journal of Clinical Investigation·Pavitra RoychoudhuryJoshua T Schiffer
Mar 22, 2019·Frontiers in Immunology·Naomi R TruongAnthony L Cunningham
May 5, 2018·Frontiers in Medicine·Tara K SigdelMinnie M Sarwal
Oct 4, 2019·British Medical Bulletin·B A KrishnaJ H Sinclair
Aug 30, 2017·Frontiers in Immunology·Angello R Retamal-DíazPablo A González
Nov 6, 2018·Frontiers in Microbiology·Francisco J IbáñezPablo A González
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Aug 26, 2020·Expert Review of Clinical Pharmacology·Kimia KardaniAzam Bolhassani
Nov 21, 2020·Viruses·Jacek BajGrzegorz Teresiński
Apr 10, 2020·Translational Research : the Journal of Laboratory and Clinical Medicine·Kevin EganHarvey M Friedman
May 18, 2021·Frontiers in Immunology·Yuqing LiWeijie Dong

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Methods Mentioned

BETA
biopsies
ELISA
dot blot
PCR
flow cytometry

Software Mentioned

FlowJo
ExPASy
LALIGN
GraphPad Prism

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