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

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 roun...

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Main Authors:	Petro, Christopher, González, Pablo A, Cheshenko, Natalia, Jandl, Thomas, Khajoueinejad, Nazanin, Bénard, Angèle, Sengupta, Mayami, Herold, Betsy C, Jacobs, William R
Format:	Online
Language:	English
Published:	eLife Sciences Publications, Ltd 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4352706/

id	pubmed-4352706
recordtype	oai_dc
spelling	pubmed-43527062015-03-13 Herpes simplex type 2 virus deleted in glycoprotein D protects against vaginal, skin and neural disease Petro, Christopher González, Pablo A Cheshenko, Natalia Jandl, Thomas Khajoueinejad, Nazanin Bénard, Angèle Sengupta, Mayami Herold, Betsy C Jacobs, William R Microbiology and Infectious Disease 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. eLife Sciences Publications, Ltd 2015-03-10 /pmc/articles/PMC4352706/ /pubmed/25756612 http://dx.doi.org/10.7554/eLife.06054 Text en © 2015, Petro et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Petro, Christopher González, Pablo A Cheshenko, Natalia Jandl, Thomas Khajoueinejad, Nazanin Bénard, Angèle Sengupta, Mayami Herold, Betsy C Jacobs, William R
spellingShingle	Petro, Christopher González, Pablo A Cheshenko, Natalia Jandl, Thomas Khajoueinejad, Nazanin Bénard, Angèle Sengupta, Mayami Herold, Betsy C Jacobs, William R Herpes simplex type 2 virus deleted in glycoprotein D protects against vaginal, skin and neural disease
author_facet	Petro, Christopher González, Pablo A Cheshenko, Natalia Jandl, Thomas Khajoueinejad, Nazanin Bénard, Angèle Sengupta, Mayami Herold, Betsy C Jacobs, William R
author_sort	Petro, Christopher
title	Herpes simplex type 2 virus deleted in glycoprotein D protects against vaginal, skin and neural disease
title_short	Herpes simplex type 2 virus deleted in glycoprotein D protects against vaginal, skin and neural disease
title_full	Herpes simplex type 2 virus deleted in glycoprotein D protects against vaginal, skin and neural disease
title_fullStr	Herpes simplex type 2 virus deleted in glycoprotein D protects against vaginal, skin and neural disease
title_full_unstemmed	Herpes simplex type 2 virus deleted in glycoprotein D protects against vaginal, skin and neural disease
title_sort	herpes simplex type 2 virus deleted in glycoprotein d protects against vaginal, skin and neural disease
description	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.
publisher	eLife Sciences Publications, Ltd
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4352706/
_version_	1613196289320681472

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

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