Virus Neutralizing Activity Induced by Synthetic Peptides of Glycoprotein D of Herpes Simplex Virus Type 1, selected by their Reactivity with Hyperimmune Sera from Mice

Geerligs, H.J.; Kocken, Clemens H. M.; Drijfhout, Jan W.; Weijer, Wicher J.; Bloemhoff, W.; Wilterdink, J. B.; Welling, Gjalt W.; Welling‐Wester, Sytske

doi:10.1099/0022-1317-71-8-1767

Cited by 16 publications

(7 citation statements)

References 36 publications

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“…The serum dilution factor that neutralized 50% of the virus was determined as the titer. The TCID 50 was 0.69 pfu as determined by the procedure described by Reed and Muench [16]. Each serum sample was assayed in triplicate.…”

Section: Methodsmentioning

confidence: 99%

Design and evaluation of a multi-epitope assembly Peptide (MEAP) against herpes simplex virus type 2 infection in BALB/c mice

Xingsheng

Xie

Liao

et al. 2011

Virol J

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BackgroundHuman herpes simplex virus (HSV) 1 and 2 causes oral, ocular, or genital infections, which remains a significant health problem worldwide. HSV-1 and -2 infections in humans range from localized skin infections of the oral, ocular, and genital regions to severe and often disseminated infections in immunocompromised hosts. Epitope based vaccination is a promising mean to achieve protective immunity and to avoid infections with Human herpes simplex virus type 2 (HSV-2).MethodsThe twelve selected epitopes, six B cell epitopes from different glycoprotein of HSV-2 (amino acid residues 466-473 (EQDRKPRN) from envelope glycoprotein B, 216-223 (GRTDRPSA) from C, 6-18 (DPSLKMADPNRFR) from D, 483-491 (DPPERPDSP) from E, 572-579 (EPPDDDDS) from G and 286-295 (CRRRYRRPRG) from I glycoprotein of HSV-2), four CD4+ T cell epitopes (amino acid residues 21-28 (NLPVLDQL) from D, 162-177 (KDVTVSQVWFGHRYSQ) from B, 205-224 (KAYQQGVTVDSIGMLPRFIP) from D and 245-259 (KPPYTSTLLPPELSD) from D) and two CD8+ T cell epitopes (amino acid residues 10-20 (KMADPNRFRGK) from D and 268-276 (ALLEDPAGT) from D), are responsible for the elicitation of the neutralizing antibodies and cytotoxic T lymphocytes (CTLs) that impart protective immunity to the host. In this study, all above epitopes were inserted into the extracellular fragment (amino acid residues 1-290) of HSV-2 glycoprotein D to construct multi-epitope assembly peptides (MEAPs) by replacing some non-epitope amino acid sequences. The epitope independency of the MEAPs was predicted by three-dimensional software algorithms. The gene of the selected MEAP was expressed in E.coli BL21(DE3), and its protective efficacy against HSV-2 infection was assessed in BALB/c mice.ResultsThe MEAP, with each inserted epitopes independently displayed on the molecule surface, was selected as candidate proteins. The results showed that the MEAP was highly immunogenic and could elicit high titer neutralizing antibodies and cell-mediated immune responses.ConclusionsThe MEAP provided complete protection against infection with HSV-2 in mice, which indicates that it might be a potential candidate vaccine against HSV-2.

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Section: Methodsmentioning

confidence: 99%

Design and evaluation of a multi-epitope assembly Peptide (MEAP) against herpes simplex virus type 2 infection in BALB/c mice

Xingsheng

Xie

Liao

et al. 2011

Virol J

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“…The gD envelope protein (59kDa) (ectodomain 36.2kDa) has been the focus of much attention because it has been shown to elicit neutralizing antibodies, and serves as a target for cellular immune responses in animal models [11], [12], [13] and more importantly, in humans [14]. The cellular immune response is believed to be a critical component for providing protection against both primary and recurrent disease [15], [16], [17], [18], [19].…”

Section: Introductionmentioning

confidence: 99%

Liposomal gD ectodomain (gD1–306) vaccine protects against HSV2 genital or rectal infection of female and male mice

Olson

Macias

Hutton

et al. 2009

Vaccine

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Herpes simplex virus type 2 (HSV2) is the most common causative agent of genital herpes, with infection rates as high as 1 in 6 adults. The present studies were done to evaluate the efficacy of a liposomal HSV2 gD1-306 vaccine (L-gD1-306-HD) in an acute murine HSV2 infection model of intravaginal (female) or intrarectal (male or female) challenge. Two doses of L-gD1-306-HD containing 60μg gD1-306-HD and 15μg monophosphoryl lipid A (MPL) per dose provided protection against HSV2 intravaginal challenge (86-100% survival, P≤0.0003 vs control liposomes; P=0.06 vs L-gD1-306-HD without MPL). Both male and female mice (BALB/c and C57BL/6) immunized with L-gD1-306-HD/MPL were significantly protected against HSV2 intrarectal challenge, with higher survival rates compared to controls (71-100%, P≤0.007). L-gD1-306-HD/MPL also provided increased survival when compared to a liposomal peptide vaccine, L-gD264-285-HD/MPL (male BALB/c, P≤0.001; female BALB/c and male C57BL/6, P=0.06). Mice given L-gD1-306-HD/MPL also had minimal disease signs, reduced viral burden in their spinal cords and elevated neutralizing antibody titers in the females. The vaccine also stimulated gD1-306-HD specific splenocytes of both male and female mice with significantly elevated levels of IFN-γ compared to IL-4 (P≤0.01) indicating that there was an enhanced Th1 response. These results provide the first evidence that the L-gD1-306–HD vaccine can protect both male and female mice against intrarectal HSV2 challenge.

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“…However, neutralizing antibodies directed against this region could not be detected in antisera fi'om mice immunized with synthetic peptides covering the C-terminal part of gD [2]. The lymphocyte proliferation data show that lymphocytes from 90% of the volunteers responded to this particular gD region (residues 290 to 369, except for the transmembrane region); only lymphocytes from volunteer t0 were not stimulated by peptides in this region.…”

Section: R a D A M H O F E T A L T A B L E 1 P R O L I F E R Amentioning

confidence: 63%

T cell responses to synthetic peptides of herpes simplex virus type 1 glycoprotein D in naturally infected individuals

Damhof

Drijfhout

Scheffer

et al. 1993

Archives of Virology

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To locate T cell determinants of glycoprotein D (gD) of herpes simplex virus type 1 (HSV-1), proliferation assays of lymphocytes obtained from 10 healthy HSV-seropositive individuals were performed using 34 overlapping gD peptides as antigens. Despite large differences between individual responses to the peptides both in number of stimulating peptides and gD regions, three regions (1-54, 110-214, and 290-314) induced a response in 50% or more of the HSV-seropositives. T cells were less frequently stimulated by peptides of region 210-294. No correlation was found between serological data and proliferative responses to the peptides. The diversity in T cell response to the peptides suggests a lack of immunodominance, implying that a single peptide/region of gD, or a combination of peptides, will not be sufficient to serve as a basis for a future HSV-1 vaccine.

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Virus Neutralizing Activity Induced by Synthetic Peptides of Glycoprotein D of Herpes Simplex Virus Type 1, selected by their Reactivity with Hyperimmune Sera from Mice

Cited by 16 publications

References 36 publications

Design and evaluation of a multi-epitope assembly Peptide (MEAP) against herpes simplex virus type 2 infection in BALB/c mice

Design and evaluation of a multi-epitope assembly Peptide (MEAP) against herpes simplex virus type 2 infection in BALB/c mice

Liposomal gD ectodomain (gD1–306) vaccine protects against HSV2 genital or rectal infection of female and male mice

T cell responses to synthetic peptides of herpes simplex virus type 1 glycoprotein D in naturally infected individuals

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