Immunogenicity of purified glycoprotein gB of herpes simplex virus

Kino, Yoichiro; Eto, Tetsuya; Nishiyama, Kiyoto; Ohtomo, Nobuya; Mori, Ryoichi

doi:10.1007/bf01309880

Cited by 16 publications

(14 citation statements)

References 26 publications

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“…Envelope protein gB has been shown to induce strong T cell responses in humans (15) (as well as neutralizing antibody [1]). In small-animal models, gB vaccination induced protection from HSV-2 challenge (14). Also, CD8 T cell responses to gB have been shown to control latency and prevent reactivation from dorsal root ganglia in mice infected with HSV-2 (11).…”

mentioning

confidence: 99%

Single and Combination Herpes Simplex Virus Type 2 Glycoprotein Vaccines Adjuvanted with CpG Oligodeoxynucleotides or Monophosphoryl Lipid A Exhibit Differential Immunity That Is Not Correlated to Protection in Animal Models

Khodai

Chappell

Christy

et al. 2011

Clin. Vaccine Immunol.

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Despite several attempts to develop an effective prophylactic vaccine for HSV-2, all have failed to show efficacy in the clinic. The most recent of these failures was the GlaxoSmithKline (GSK) subunit vaccine based on the glycoprotein gD with the adjuvant monophosphoryl lipid A (MPL). In a phase 3 clinical trial, this vaccine failed to protect from HSV-2 disease, even though good neutralizing antibody responses were elicited. We aimed to develop a superior, novel HSV-2 vaccine containing either gD or gB alone or in combination, together with the potent adjuvant CpG oligodeoxynucleotides (CPG). The immunogenic properties of these vaccines were compared in mice. We show that gB/CPG/alum elicited a neutralizing antibody response similar to that elicited by gD/CPG/alum vaccine but a significantly greater gamma interferon (IFN-␥) T cell response. Furthermore, the combined gB-gD/CPG/alum vaccine elicited significantly greater neutralizing antibody and T cell responses than gD/MPL/alum. The efficacies of these candidate vaccines were compared in the mouse and guinea pig disease models, including a novel male guinea pig genital disease model. These studies demonstrated that increased immune response did not correlate to improved protection. First, despite a lower IFN-␥ T cell response, the gD/CPG/alum vaccine was more effective than gB/CPG/alum in mice. Furthermore, the gB-gD/CPG/alum vaccine was no more effective than gD/MPL/alum in mice or male guinea pigs. We conclude that difficulties in correlating immune responses to efficacy in animal models will act as a deterrent to researchers attempting to develop effective HSV vaccines.

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confidence: 99%

Single and Combination Herpes Simplex Virus Type 2 Glycoprotein Vaccines Adjuvanted with CpG Oligodeoxynucleotides or Monophosphoryl Lipid A Exhibit Differential Immunity That Is Not Correlated to Protection in Animal Models

Khodai

Chappell

Christy

et al. 2011

Clin. Vaccine Immunol.

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“…In earlier studies, other workers producing HSV antigen preparations for possible use as vaccines in man and employing NP40 or Triton-X-100 detergents [5,17,24,28,41], have for the most part, not reported which HSV glycoproteins are present in their preparations. The Empigen-extracted SDG preparations described in the present study have been shown to contain four HSV-1 gtycoproteins gB, gC, gD and gE, some of which have been found, as individual glycoproteins, to provide protections in animals against HSV challenge [11,20,25,37,39]. Further characterisation of these SDG preparations with respect to the total number and nature of the proteins present, using Western blotting and radioimmunoprecipitation, are currently underway.…”

Section: Discussionmentioning

confidence: 89%

“…Although vaccines containing a number of surface and perhaps internally located HSV proteins may be required to provide protection against infection, several workers have investigated the possibility of using individual surface glycoproteins as vaccines [7,11,20,25,37,39]. The reason for this is the need for highly-purified preparations in man, and undoubtedly HSV antigen preparations obtained by detergent-extractions from infected cells, will contain unwanted proteins and perhaps other materials, including DNA.…”

Section: Discussionmentioning

confidence: 98%

“…Amongst a number of different approaches [10,14,16,22], has been the conventional detergent extraction and subsequent purification of viral surface glycoproteins in an immunogenic form from purified whole virus particles [5,18] or from virus-infected cells [21,24,28,41]. In addition, a number of workers have purified individual glycoproteins from HSV strains and demonstrated that such preparations can provide protection in animals [7,11,20,25,37,38].…”

Section: Introductionmentioning

confidence: 99%

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Zwitterionic detergent solubilisation of HSV-1 surface antigens

Jennings

Quasim

Sharrard

et al. 1988

Archives of Virology

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A preparation was obtained from herpes simplex virus type 1 (HSV-1)-infected cells using a zwitterionic detergent, Empigen BB. The preparation was partially-purified either by ultracentrifugation over a cusion of 20% sucrose or on a sucrose density gradient. Partial characterisation of these materials by ELISA, using both polyclonal and monoclonal antibodies showed them to contain at least four major HSV glycoproteins, gB, gC, gD and gE. Comparison of Empigen-extracted HSV-1 antigen preparations with preparations obtained using the non-ionic detergents Nonidet P40 or Triton-X-100 indicate that, using conventional procedures, separation of glycoproteins, B, C, D, and E from unwanted proteins may be facilitated using the former detergent. Immunization of mice with Empigen-extracted, partially-purified or gradient-purified antigen preparations elicited good levels of antibody detectable by ELISA and a high degree of protection against both HSV-1 and HSV-2 challenge infection. Such protection could be achieved using aqueous antigen preparations, but was augmented using aluminium hydroxide gel as an adjuvant. In general, Empigen-extracted HSV-1 antigen preparations elicited higher ELISA antibody levels and more complete protection against HSV challenge infection than NP40 or Triton-X-100-extracted preparations. The value and usefulness of the detergent Empigen for obtaining HSV surface antigen preparations and the role of these as potential vaccines against HSV infections, is discussed.

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“…To improve the immune response, a subunit vaccine containing gC and gD antigens could be supplemented with recombinant gB, which has been shown to be effective in the mouse model system both by active and by passive immunization (Kino et al 1985(Kino et al , 1986. Since gB seems to carry predominantly nonsequencial epitopes, which are responsible for the immune response (Chapsal and Pereira 1988), this protein might, as expected for gC, be expressed immunogenically in eukaryotic cells rather than in bacteria (Pachl et al 1987;Blacklows et al 1987;Kino et al 1989).…”

Section: Discussionmentioning

confidence: 99%

Escherichia coli-derived envelope protein gD but not gC antigens of herpes simplex virus protect mice against a lethal challenge with HSV-1 and HSV-2

Bröker

Abel

Köhler

et al. 1990

Med Microbiol Immunol

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Immunization studies with HSV-1 and HSV-2 envelope proteins expressed in Escherichia coli were performed. After active immunization of mice with a gD-1 antigen (Leu53-Ala312) expressed as a fusion protein, the animals were protected from a lethal challenge with HSV-1 and HSV-2. In addition, antisera from rabbits immunized with the same gD-1 antigen also conferred passive immunity to mice against a challenge infection with either HSV-1 or HSV-2. In contrast to these successful gD-1 protection experiments, various gC-1 and gC-2 fusion proteins from E. coli failed to induce protective immunity. Moreover, the mice sera from immunized animals were not able to react with the authentic, glycosylated gC-1 and gC-2 envelope proteins, whereas sera raised against authentic gC-1 and gC-2 glycoproteins do recognize the gC fusion proteins from E. coli. These results indicate, that E. coli might represent an ideal system for expressing gD antigens as a possible component of a HSV vaccine, whereas gC antigen cannot be produced in an immunocompetent form in E. coli.

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Immunogenicity of purified glycoprotein gB of herpes simplex virus

Cited by 16 publications

References 26 publications

Single and Combination Herpes Simplex Virus Type 2 Glycoprotein Vaccines Adjuvanted with CpG Oligodeoxynucleotides or Monophosphoryl Lipid A Exhibit Differential Immunity That Is Not Correlated to Protection in Animal Models

Single and Combination Herpes Simplex Virus Type 2 Glycoprotein Vaccines Adjuvanted with CpG Oligodeoxynucleotides or Monophosphoryl Lipid A Exhibit Differential Immunity That Is Not Correlated to Protection in Animal Models

Zwitterionic detergent solubilisation of HSV-1 surface antigens

Escherichia coli-derived envelope protein gD but not gC antigens of herpes simplex virus protect mice against a lethal challenge with HSV-1 and HSV-2

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