Multi-antigenic DNA immunization using herpes simplex virus type 2 genomic fragments

Braun, Ralph P.; Dong, Lichun; Jerome, Sarah; Herber, Renee; Roberts, Lee K.; Payne, Lendon G.

doi:10.4161/hv.4.1.4876

Cited by 8 publications

(2 citation statements)

References 17 publications

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“…Hence, it can be postulated that when the CDVH native valence was expressed in the same cell as GPV, it was able to induce a cross boost effect. Similar results have been reported when a mixture of antigens was used [25,26]. This can be explained by the induction of a more robust cytokine environment since it is reported that DNA-based vaccination is highly efficient in inducing T cell responses [27].…”

Section: Discussionsupporting

confidence: 83%

Design of different strategies of multivalent DNA-based vaccination against rabies and canine distemper in mice and dogs

Touihri

Ahmed

Chtourou

et al. 2012

Virol J

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BackgroundDuring the vaccination campaigns, puppies younger than 3 months old are not targeted and remain unvaccinated for at least the first year of their lives. Almost half of the reported rabid dogs are 6 months or younger. Hence, we should recommend the vaccination against rabies of young puppies. Unfortunately, owing to the exposure of puppies to infections with either canine parvovirus (CPV) or distemper virus (CDV) after the intervention of the vaccinators, owners are reluctant to vaccinate puppies against rabies. Therefore, it is necessary to include the CPV and CDV valences in the vaccine against rabies. Multivalent DNA-based vaccination in dogs, including rabies and distemper valences, could help in raising vaccine coverage.MethodsWe have designed monovalent and multivalent DNA-based vaccine candidates for in vitro and in vivo assays. These plasmids encode to the rabies virus glycoprotein and/or the canine distemper virus hemagglutinin. The first strategy of multivalent DNA-based vaccination is by mixing plasmids encoding to a single antigen each. The second is by simply fusing the genes of the antigens together. The third is by adding the foot and mouth disease virus (FMDV) 2A oligopeptide gene into the antigen genes. The last strategy is by the design and use of a bicistronic plasmid with an “Internal Ribosome Entry Site” (IRES) domain.ResultsThe monovalent construct against canine distemper was efficiently validated by inducing higher humoral immune responses compared to cell-culture-derived vaccine both in mice and dogs. All multivalent plasmids efficiently expressed both valences after in vitro transfection of BHK-21 cells. In BALB/c mice, the bicistronic IRES-dependant construct was the most efficient inducer of virus-neutralizing antibodies against both valences. It was able to induce better humoral immune responses compared to the administration of either cell-culture-derived vaccines or monovalent plasmids. The FMDV 2A was also efficient in the design of multivalent plasmids.ConclusionsIn a single shot, the design of efficient multivalent plasmids will be very beneficial for DNA-based vaccination against numerous diseases.

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Section: Discussionsupporting

confidence: 83%

Design of different strategies of multivalent DNA-based vaccination against rabies and canine distemper in mice and dogs

Touihri

Ahmed

Chtourou

et al. 2012

Virol J

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“…(19,57). Limited studies to characterize the cellular responses elicited by ICP4 in mice have been performed (58,59). Martin et al (59) showed that HSVspecific T cells lysed ICP4-expressing target cells in vitro, but none of the immunized mice generated antigen-specific cytotoxic T cell responses.…”

Section: Discussionmentioning

confidence: 99%

An Adjuvanted Herpes Simplex Virus 2 Subunit Vaccine Elicits a T Cell Response in Mice and Is an Effective Therapeutic Vaccine in Guinea Pigs

Škoberne

Cardin

Lee

et al. 2013

J Virol

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bImmunotherapeutic herpes simplex virus 2 (HSV-2) vaccine efficacy depends upon the promotion of antigen-specific immune responses that inhibit reactivation or reactivated virus, thus controlling both recurrent lesions and viral shedding. In the present study, a candidate subunit vaccine, GEN-003/MM-2, was evaluated for its ability to induce a broad-spectrum immune response in mice and therapeutic efficacy in HSV-2-infected guinea pigs. GEN-003 is comprised of HSV-2 glycoprotein D2 (gD2⌬TMR 340-363 ) and a truncated form of infected cell polypeptide 4 (ICP4 383-766 ), formulated with Matrix M-2 (MM-2) adjuvant (GEN-003/MM-2). In addition to eliciting humoral immune responses, CD4؉ and CD8 ؉ T cells characterized by the secretion of multiple cytokines and cytolytic antigen-specific T cell responses that were able to be recalled at least 44 days after the last immunization were induced in immunized mice. Furthermore, vaccination with either GEN-003 or GEN-003/MM-2 led to significant reductions in both the prevalence and severity of lesions in HSV-2-infected guinea pigs compared to those of phosphate-buffered saline (PBS) control-vaccinated animals. While vaccination with MM-2 adjuvant alone decreased recurrent disease symptoms compared to the PBS control group, the difference was not statistically significant. Importantly, the frequency of recurrent viral shedding was considerably reduced in GEN-003/MM-2-vaccinated animals but not in GEN-003-or MM-2-vaccinated animals. These findings suggest a possible role for immunotherapeutic GEN-003/MM-2 vaccination as a viable alternative to chronic antiviral drugs in the treatment and control of genital herpes disease. H erpes simplex virus 2 (HSV-2) is one of the most prevalent sexually transmitted diseases, having infected more than 500 million people worldwide, with an estimated 23 million new infections occurring annually (1). HSV-2 infects epithelial cells of the genital mucosa during primary infection, followed by the establishment of latency in neuronal dorsal root ganglia via retrograde transport along nerve axons. Throughout latency, virus can reactivate, causing genital lesions and/or asymptomatic shedding of virus. Although suppressive antiviral therapy has shown promise in reducing both symptomatic recurrent lesions and overall viral shedding, subclinical HSV reactivation persists, likely contributing significantly to the observed continued transmission (2). The development of an efficacious immunotherapeutic vaccine targeting HSV-2 likely represents the best strategy for preventing both lesion outbreaks and the continued spread of virus.Despite considerable effort, all vaccine candidates to date have failed to meet their defined endpoints in clinical trials. The majority of clinical trials to date have focused on prophylactic subunit vaccines, largely using the HSV-2 surface glycoproteins as immunogens. The viral envelope glycoproteins gD and gB are the dominant targets for neutralizing antibody production (3, 4), making them logical candidates for vaccine devel...

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Vaccine Delivery

Sahni¹,

Cheng²,

Middaugh³

et al. 2016

Drug Delivery

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Multi-antigenic DNA immunization using herpes simplex virus type 2 genomic fragments

Cited by 8 publications

References 17 publications

Design of different strategies of multivalent DNA-based vaccination against rabies and canine distemper in mice and dogs

Design of different strategies of multivalent DNA-based vaccination against rabies and canine distemper in mice and dogs

An Adjuvanted Herpes Simplex Virus 2 Subunit Vaccine Elicits a T Cell Response in Mice and Is an Effective Therapeutic Vaccine in Guinea Pigs

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