Efficacy of the herpes simplex virus 2 (HSV-2) glycoprotein D/AS04 vaccine against genital HSV-2 and HSV-1 infection and disease in the cotton rat Sigmodon hispidus model

Marina Boukhvalova, Jamall McKay, Aissatou Mbaye, Hannah Sanford-Crane, Jorge C G Blanco, Ashley Huber, Betsy Herold

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Subunit vaccines based on the herpes simplex virus 2 (HSV-2) glycoprotein D (gD-2) have been the major focus of HSV-2 vaccine development for the past 2 decades. Based on the promising data generated in the guinea pig model, a formulation containing truncated gD-2, aluminum salt, and MPL (gD/AS04) advanced to clinical trials. The results of these trials, however, were unexpected, as the vaccine protected against HSV-1 infection but not against HSV-2. To address this discrepancy, we developed a Depot medroxyprogesterone acetate (DMPA)-treated cotton rat Sigmodon hispidus model of HSV-2 and HSV-1 genital infection. The severity of HSV-1 genital herpes was less than that of HSV-2 genital herpes in cotton rats, and yet the model allowed for comparative evaluation of gD/AS04 immunogenicity and efficacy. Cotton rats were intramuscularly vaccinated using a prime boost strategy with gD/AS04 (Simplirix vaccine) or control vaccine formulation (hepatitis B vaccine FENDrix) and subsequently challenged intravaginally with HSV-2 or HSV-1. The gD/AS04 vaccine was immunogenic in cotton rats and induced serum IgG directed against gD-2 and serum HSV-2 neutralizing antibodies but failed to efficiently protect against HSV-2 disease or to decrease the HSV-2 viral load. However, gD/AS04 significantly reduced vaginal titers of HSV-1 and better protected animals against HSV-1 compared to HSV-2 genital disease. The latter finding is generally consistent with the clinical outcome of the Herpevac trial of Simplirix. Passive transfer of serum from gD/AS04-immunized cotton rats conferred stronger protection against HSV-1 genital disease. These findings suggest the need for alternative vaccine strategies and the identification of new correlates of protection.

Original languageEnglish (US)
Pages (from-to)9825-9840
Number of pages16
JournalJournal of Virology
Volume89
Issue number19
DOIs
StatePublished - 2015
Externally publishedYes

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Sigmodon
Human herpesvirus 2
Sigmodon hispidus
Sigmodontinae
Herpes Genitalis
Human Herpesvirus 2
Human Herpesvirus 1
genitalia
glycoproteins
Vaccines
vaccines
Infection
infection
Herpes Simplex Virus Vaccines
Serum
glycoprotein D-herpes simplex virus type 2
Hepatitis B Vaccines
Medroxyprogesterone Acetate
medroxyprogesterone
Subunit Vaccines

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Efficacy of the herpes simplex virus 2 (HSV-2) glycoprotein D/AS04 vaccine against genital HSV-2 and HSV-1 infection and disease in the cotton rat Sigmodon hispidus model. / Boukhvalova, Marina; McKay, Jamall; Mbaye, Aissatou; Sanford-Crane, Hannah; Blanco, Jorge C G; Huber, Ashley; Herold, Betsy.

In: Journal of Virology, Vol. 89, No. 19, 2015, p. 9825-9840.

Research output: Contribution to journalArticle

Boukhvalova, Marina ; McKay, Jamall ; Mbaye, Aissatou ; Sanford-Crane, Hannah ; Blanco, Jorge C G ; Huber, Ashley ; Herold, Betsy. / Efficacy of the herpes simplex virus 2 (HSV-2) glycoprotein D/AS04 vaccine against genital HSV-2 and HSV-1 infection and disease in the cotton rat Sigmodon hispidus model. In: Journal of Virology. 2015 ; Vol. 89, No. 19. pp. 9825-9840.
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