title: Current status and prospects for development of an HSV vaccine.
abstract: Herpes simplex virus type 2 (HSV-2) infects 530million people, is the leading cause of genital ulcer disease, and increases the risk of HIV-1 acquisition. Although several candidate vaccines have been promising in animal models, prophylactic and therapeutic vaccines have not been effective in clinical trials thus far. Null results from the most recent prophylactic glycoprotein D2 subunit vaccine trial suggest that we must reevaluate our approach to HSV-2 vaccine development. We discuss HSV-2 pathogenesis, immunity, and vaccine efforts to date, as well as the current pipeline of candidate vaccines and design of trials to evaluate new vaccine constructs.
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA, United States; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States. Electronic address: cjohnsto@u.washington.edu.
authors.forename: Christine
authors.initials: C
authors.lastname: Johnston
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA, United States; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States; Department of Laboratory Medicine, University of Washington, Seattle, WA, United States; Department of Global Health, University of Washington, Seattle, WA, United States; Benaroya Research Institute, Seattle, WA, United States.
authors.forename: David M
authors.initials: DM
authors.lastname: Koelle
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA, United States; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States; Department of Laboratory Medicine, University of Washington, Seattle, WA, United States; Department of Epidemiology, University of Washington, Seattle, WA, United States.
authors.forename: Anna
authors.initials: A
authors.lastname: Wald
mesh_terms: D000818:Animals; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006558:Herpes Genitalis / Q000276:immunology / Q000517:prevention & control*; D022301:Herpes Simplex Virus Vaccines / Q000276:immunology* / Q000627:therapeutic use; D018258:Herpesvirus 2, Human; D006801:Humans; D018928:Immunity, Mucosal; D014611:Vaccination / Q000639:trends; D022223:Vaccines, Subunit / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D022301:Herpes Simplex Virus Vaccines; D022223:Vaccines, Subunit; D014759:Viral Envelope Proteins; C040570:glycoprotein D-herpes simplex virus type 2
keywords: Genital herpes; Herpes simplex virus; Vaccine
references.citation: Sex Transm Dis. 2011 Sep;38(9):837-44
references.pmid: 21844740
references.citation: Lancet. 2012 Feb 18;379(9816):641-7
references.pmid: 22225814
references.citation: J Virol. 2000 Sep;74(17):7963-71
references.pmid: 10933704
references.citation: J Virol. 2011 Apr;85(7):3461-72
references.pmid: 21270160
references.citation: J Infect Dis. 2009 Oct 1;200(7):1088-95
references.pmid: 19702506
references.citation: Vaccine. 2012 Jun 19;30(29):4361-8
references.pmid: 22682292
references.citation: Bull World Health Organ. 2008 Oct;86(10):805-12, A
references.pmid: 18949218
references.citation: Sci Transl Med. 2009 Nov 18;1(7):7ra16
references.pmid: 20161655
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3496-501
references.pmid: 17360672
references.citation: J Clin Invest. 2012 Feb;122(2):654-73
references.pmid: 22214845
references.citation: J Infect Dis. 2003 May 15;187(10):1513-21
references.pmid: 12721931
references.citation: J Virol. 2012 Sep;86(18):9952-63
references.pmid: 22761381
references.citation: J Infect Dis. 2005 May 15;191(10):1734-46
references.pmid: 15838802
references.citation: J Virol. 2005 Dec;79(23):14632-9
references.pmid: 16282463
references.citation: Vaccine. 2009 Feb 5;27(6):940-6
references.pmid: 19071187
references.citation: J Infect Dis. 2000 Sep;182(3):923-7
references.pmid: 10950790
references.citation: Lancet. 1994 Jun 11;343(8911):1460-3
references.pmid: 7911177
references.citation: Vaccine. 2010 Nov 3;28(47):7483-91
references.pmid: 20851091
references.citation: Hum Immunol. 2012 Aug;73(8):844-51
references.pmid: 22537752
references.citation: Vaccine. 2006 Feb 13;24(7):914-20
references.pmid: 16213066
references.citation: PLoS One. 2013;8(2):e57224
references.pmid: 23468943
references.citation: Ann Intern Med. 1995 Jun 15;122(12):889-98
references.pmid: 7755223
references.citation: J Virol. 2012 Oct;86(19):10587-96
references.pmid: 22811543
references.citation: J Virol. 2012 Apr;86(8):4358-69
references.pmid: 22318137
references.citation: N Engl J Med. 1997 Aug 21;337(8):509-15
references.pmid: 9262493
references.citation: Nature. 2012 Nov 15;491(7424):463-7
references.pmid: 23075848
references.citation: J Infect Dis. 1982 Sep;146(3):397-404
references.pmid: 6286797
references.citation: Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12899-904
references.pmid: 14566059
references.citation: J Gen Virol. 2012 Aug;93(Pt 8):1717-1724
references.pmid: 22552940
references.citation: J Immunol. 2010 Mar 1;184(5):2243-6
references.pmid: 20124105
references.citation: J Virol. 2008 Dec;82(23):11792-802
references.pmid: 18799581
references.citation: Arch Intern Med. 2009 Jul 13;169(13):1233-40
references.pmid: 19597073
references.citation: J Clin Invest. 2011 Dec;121(12):4600-9
references.pmid: 22133885
references.citation: N Engl J Med. 2009 Mar 26;360(13):1298-309
references.pmid: 19321868
references.citation: J Clin Immunol. 2010 Sep;30(5):703-22
references.pmid: 20635156
references.citation: J Infect Dis. 2009 Apr 1;199(7):945-9
references.pmid: 19220138
references.citation: Int J Pharm. 2013 Jan 20;440(2):229-37
references.pmid: 22743007
references.citation: JAMA. 2003 Jan 8;289(2):203-9
references.pmid: 12517231
references.citation: Vaccine. 2005 Nov 16;23(46-47):5424-31
references.pmid: 15950327
references.citation: Immunity. 2013 Jan 24;38(1):176-86
references.pmid: 23313589
references.citation: J Virol. 2012 Apr;86(8):4328-39
references.pmid: 22318154
references.citation: Sex Transm Dis. 2008 Jan;35(1):19-21
references.pmid: 18157062
references.citation: J Virol. 2012 Dec;86(23):12891-902
references.pmid: 22993162
references.citation: Cell Host Microbe. 2007 Jul 12;2(1):19-28
references.pmid: 18005714
references.citation: PLoS One. 2011 Mar 11;6(3):e17748
references.pmid: 21412438
references.citation: Cutis. 2002 Oct;70(4):235-9
references.pmid: 12403316
references.citation: AIDS. 2009 Sep 10;23(14):1807-15
references.pmid: 19584700
references.citation: JAMA. 1998 Jul 1;280(1):61-6
references.pmid: 9660365
references.citation: N Engl J Med. 1999 Nov 4;341(19):1432-8
references.pmid: 10547406
references.citation: J Immunol. 2012 May 1;188(9):4412-20
references.pmid: 22490439
references.citation: J Infect Dis. 2007 Aug 15;196(4):505-9
references.pmid: 17624834
references.citation: N Engl J Med. 2004 Jan 1;350(1):11-20
references.pmid: 14702423
references.citation: Sex Transm Infect. 2004 Feb;80(1):24-9
references.pmid: 14755031
references.citation: J Acquir Immune Defic Syndr. 2007 Dec 15;46(5):631-42
references.pmid: 18043318
references.citation: J Infect Dis. 2002 Apr 15;185(8):1019-24
references.pmid: 11930310
references.citation: J Virol. 2012 Jun;86(12):6563-74
references.pmid: 22491465
references.citation: J Acquir Immune Defic Syndr. 2010 Aug;54(5):482-8
references.pmid: 20616743
references.citation: Sex Transm Infect. 2009 Oct;85(6):416-9
references.pmid: 19273479
references.citation: J Infect Dis. 2013 Nov 1;208(9):1366-74
references.pmid: 23901094
references.citation: J Infect Dis. 2011 May 15;203(10):1434-41
references.pmid: 21498376
references.citation: Vaccine. 2011 Jan 29;29(5):1090-8
references.pmid: 21134447
references.citation: J Exp Med. 2012 Aug 27;209(9):1567-82
references.pmid: 22851595
references.citation: Ann Intern Med. 1992 Feb 1;116(3):197-202
references.pmid: 1309413
references.citation: J Infect Dis. 2006 Sep 15;194 Suppl 1:S11-8
references.pmid: 16921466
references.citation: J Virol. 2012 Jun;86(11):6334-40
references.pmid: 22457520
references.citation: J Exp Med. 2007 Mar 19;204(3):595-603
references.pmid: 17325200
references.citation: Viruses. 2012 May;4(5):800-32
references.pmid: 22754650
references.citation: J Virol. 1987 Apr;61(4):1125-35
references.pmid: 3029407
references.citation: J Virol. 2011 May;85(10):5036-47
references.pmid: 21389121
references.citation: J Infect Dis. 2008 Oct 15;198(8):1141-9
references.pmid: 18783315
references.citation: Vaccine. 2012 Nov 19;30(49):7046-51
references.pmid: 23041125
references.citation: Infect Immun. 1982 Sep;37(3):1132-7
references.pmid: 6290390
references.citation: N Engl J Med. 2012 Jan 5;366(1):34-43
references.pmid: 22216840
references.citation: J Virol. 2013 Apr;87(7):3930-42
references.pmid: 23365421
references.citation: JAMA. 2006 Aug 23;296(8):964-73
references.pmid: 16926356
references.citation: J Clin Invest. 2002 Aug;110(4):537-48
references.pmid: 12189248
references.citation: JAMA. 1999 Jul 28;282(4):331-40
references.pmid: 10432030
references.citation: J Infect Dis. 2006 Jul 1;194(1):42-52
references.pmid: 16741881
references.citation: Sex Transm Dis. 2013 Mar;40(3):197-201
references.pmid: 23403600
references.citation: Sex Transm Infect. 2007 Feb;83(1):16-22
references.pmid: 17098770
references.citation: J Infect Dis. 2000 Sep;182(3):662-70
references.pmid: 10950757
references.citation: J Clin Invest. 1998 Apr 1;101(7):1500-8
references.pmid: 9525993
references.citation: Vaccine. 2012 Oct 12;30(46):6541-6550
references.pmid: 22947141
references.citation: J Virol. 2005 Jan;79(1):410-8
references.pmid: 15596834
references.citation: Front Microbiol. 2012 Apr 30;3:158
references.pmid: 22557998
references.citation: PLoS One. 2009 Nov 30;4(11):e8060
references.pmid: 20011586
references.citation: J Infect Dis. 2002 Jan 1;185(1):45-52
references.pmid: 11756980
references.citation: Proc Natl Acad Sci U S A. 2010 Nov 2;107(44):18973-8
references.pmid: 20956313
references.citation: Pediatrics. 2001 Aug;108(2):223-9
references.pmid: 11483781
references.citation: J Virol. 2012 Apr;86(8):4586-98
references.pmid: 22318147
references.citation: J Infect Dis. 1997 Nov;176(5):1129-34
references.pmid: 9359709
references.citation: Lancet. 2001 Apr 14;357(9263):1149-53
references.pmid: 11323041
references.citation: J Virol. 2013 Jan;87(1):474-81
references.pmid: 23097453
references.citation: Nat Med. 2009 Aug;15(8):886-92
references.pmid: 19648930
references.citation: N Engl J Med. 2002 Nov 21;347(21):1652-61
references.pmid: 12444179
references.citation: J Immunol. 2011 Apr 1;186(7):3927-33
references.pmid: 21357536
references.citation: AIDS. 2007 Mar 12;21(5):589-98
references.pmid: 17314521
references.citation: Clin Infect Dis. 2005 Nov 1;41(9):1304-12
references.pmid: 16206106
references.citation: Virology. 2010 Sep 30;405(2):269-79
references.pmid: 20598729
references.citation: J Infect Dis. 1998 Dec;178(6):1795-8
references.pmid: 9815237
references.citation: Vaccine. 2011 Nov 3;29(47):8520-9
references.pmid: 21945262
references.citation: Clin Infect Dis. 2010 Jul 15;51(2):197-213
references.pmid: 20550454
references.citation: AIDS. 2006 Jan 2;20(1):73-83
references.pmid: 16327322
references.citation: Clin Infect Dis. 2005 May 1;40(9):1271-81
references.pmid: 15825029
references.citation: J Virol. 2013 Mar;87(5):2617-27
references.pmid: 23255792
references.citation: Vaccine. 2012 Nov 20;30 Suppl 5:F123-38
references.pmid: 23199956
references.citation: Sex Transm Dis. 2010 May;37(5):290-7
references.pmid: 20351622
references.citation: Sex Transm Infect. 2005 Apr;81(2):103-7
references.pmid: 15800084
references.citation: Proc Natl Acad Sci U S A. 2012 May 1;109(18):7037-42
references.pmid: 22509047
references.citation: MMWR Morb Mortal Wkly Rep. 2010 Apr 23;59(15):456-9
references.pmid: 20414188
references.citation: JAMA. 2011 Apr 13;305(14):1441-9
references.pmid: 21486977
references.citation: J Infect Dis. 2012 Feb 1;205(3):486-90
references.pmid: 22147796