Suicidal DNA Research Articles

Genome-Wide DNA Methylation Patterns in Suicide Victims: Identification of New Candidate Genes.

Suicide is a major global public health problem with significant impact on society. According to the World Health Organization, every year about 800.000 people commit suicide, while at the global level suicide accounts for 50% of all violent deaths among men and for 71% among women. Suicide is a complex phenomenon which cannot be attributed to a single causal factor, but to a combination of simultaneous effects of multiple factors which are expressed in the form of psychological, biological and sociological indicators. Analysis of epigenetic mechanisms (methylation of the DNA, modifications of histone proteins and (networks of) miRNA), which link the interaction between genes and the environment, could importantly contribute to better understanding of suicidal behaviour. Recent studies on suicidal behaviour and DNA methylation show differences in DNA methylation pattern, with numerous sites among suicide victims. Using next generation sequencing, genome-wide studies helped identify novel candidate genes while studies of already known candidate genes (such as glucocorticoid receptor and BDNF) gave us better insight into the interplay of genetics and epigenetics. Epigenetic studies importantly contribute to elucidation of new biomarkers for suicidal behaviour. However, present studies are very different in design and often performed on very small samples, and these limitations could be overcome with more careful study preparation.

Immunization with a suicidal DNA vaccine expressing the E glycoprotein protects ducklings against duck Tembusu virus

BackgroudDuck Tembusu virus (DTMUV), a pathogenic flavivirus, emerged in China since 2010 and causing huge economic loss in the Chinese poultry industry. Although several vaccines have been reported to control DTMUV disease, few effective vaccines are available and new outbreaks were continuously reported. Thus, it is urgently to develop a new effective vaccine for prevention of this disease.MethodsIn this study, a suicidal DNA vaccine based on a Semliki Forest virus (SFV) replicon and DTMUV E glycoprotein gene was constructed and the efficacy of this new vaccine was assessed according to humoral and cell-mediated immune responses as well as protection against the DTMUV challenge in ducklings.ResultsOur results showed that the recombinant SFV replicon highly expressed E glycoprotein in DEF cells. After intramuscular injection of this new DNA vaccine in ducklings, robust humoral and cellular immune responses were observed in all immunized ducklings. Moreover, all ducklings were protected against challenge with the virulent DTMUV AH-F10 strain.ConclusionsIn conclusion, we demonstrate that this suicidal DNA vaccine is a promising candidate facilitating the prevention of DTMUV infection.

A pilot study of differential brain activation to suicidal means and DNA methylation of CACNA1C gene in suicidal attempt patients

Suicide is a serious public health problem. In this study, we investigated functional brain changes to novel visual stimuli of suicidal means, DNA methylation status, and the relationship between the two markers. 14 suicidal attempt patients (SAs) and 22 healthy controls were included. Pictures of facial expressions and suicidal means were shown to subjects during fMRI scanning. 11 CpG sites within transcription factor binding site of CACNA1C gene were selected. In knives (K) vs. natural landscape (NL) condition, left middle frontal gyrus (Brodmann's area, BA 6 and 46) and left inferior frontal gyrus (BA 9) were shown to be significantly higher brain activation in the SAs than the controls (p<0.001). DNA methylation percentages of CpG site 4 (p=0.005) and 6 (p=0.037) were found to be related to the SAs. In the SAs, methylation degree of site 4 and site 6 was positively correlated with signal intensity of K vs. NL condition in left thalamus. The degree of site 4 was positively correlated with signal intensity in left middle and inferior frontal gyri in SAs. The possibility that these findings might be involved in the neurobiology of suicidal behavior is suggested.

Protective immune response in mice induced by a suicidal DNA vaccine encoding NTPase-II gene of Toxoplasma gondii

DNA-based alphaviral RNA replicon vectors, also called suicidal DNA vectors, have been employed to alleviate biosafety concerns attribution to its ability to induce apoptotic cell death of the transfected cells. Toxoplasma gondii nucleoside triphosphate hydrolase-II (TgNTPase-II), which facilitates the parasite to salvage purines from the host cell for survival and replication, have been demonstrated to be a potential vaccine candidate for toxoplasmosis. Herein, we evaluated the immunogenic potential of a suicidal DNA vaccine encoding TgNTPase-II gene, pDREP-TgNTPase-II, delivered intramuscularly in combination with electroporation. Immunization of mice with pDREP-TgNTPase-II elicited specific humoral responses, with high IgG antibody titers and a mixed IgG1/IgG2a response. The cellular immune response was associated with high level production of IFN-γ, IL-2, IL-10 cytokines and low level IL-4 production as well as the increase of the percentage of CD8+ T cells, indicating that a Th1 predominant response was elicited. Furthermore, mice vaccinated with this suicidal DNA vaccine displayed partial protection against acute infection with the virulent RH strain as well as chronic infection with PRU cyst, which shows 77.7% and 71.4% reduction in brain cyst burden in comparison to PBS and pDREP-eGFP control group, respectively. Based on the cellular and antibody responses, the suicidal DNA vaccine elicited a Th1-predominant immune response against T. gondii challenge.

A suicidal DNA vaccine expressing the fusion protein of peste des petits ruminants virus induces both humoral and cell-mediated immune responses in mice

Peste des petits ruminants (PPR), a highly contagious disease induced by PPR virus (PPRV), affects sheep and goats. PPRV fusion (F) protein is important for the induction of immune responses against PPRV. We constructed a Semliki Forest virus (SFV) replicon-vectored DNA vaccine (“suicidal DNA vaccine”) and evaluated its immunogenicity in BALB/c mice. The F gene of PPRV was cloned and inserted into the SFV replicon-based vector pSCA1. The antigenicity of the resultant plasmid pSCA1/F was identified by indirect immunofluorescence and western blotting. BALB/c mice were then intramuscularly injected with pSCA1/F three times at 14-d intervals. Specific antibodies and virus-neutralizing antibodies against PPRV were quantified by indirect ELISA and microneutralization tests, respectively. Cell-mediated immune responses were examined by cytokine and lymphocyte proliferation assays. The pSCA1/F expressed F protein in vitro and induced specific and neutralizing antibody production, and lymphocyte proliferation in mice. Mice vaccinated with pSCA1/F had increased IL-2 and IL-10 levels after 24-h post first immunization. IFN-γ and TNF-α levels increased from that time point and gradually decreased thereafter. Thus, the Semliki Forest virus replicon-vectored DNA vaccine expressing the F protein of PPRV induced both humoral and cell-mediated immune responses in mice. This could be considered as a novel strategy for vaccine development against PPR.

Priming with two DNA vaccines expressing hepatitis C virus NS3 protein targeting dendritic cells elicits superior heterologous protective potential in mice.

Development an effective vaccine may offer an alternative preventive and therapeutic strategy against HCV infection. DNA vaccination has been shown to induce robust humoral and cellular immunity and overcome many problems associated with conventional vaccines. In this study, mice were primed with either conventional pVRC-based or suicidal pSC-based DNA vaccines carrying DEC-205-targeted NS3 antigen (DEC-NS3) and boosted with type 5 adenoviral vectors encoding the partial NS3 and core antigens (C44P). The prime boost regimen induced a marked increase in antigen-specific humoral and T-cell responses in comparison with either rAd5-based vaccines or DEC-205-targeted DNA immunization in isolation. The protective effect against heterogeneous challenge was correlated with high levels of anti-NS3 IgG and T-cell-mediated immunity against NS3 peptides. Moreover, priming with a suicidal DNA vaccine (pSC-DEC-NS3), which elicited increased TNF-α-producing CD4+ and CD8+ T-cells against NS3-2 peptides (aa 1245-1461), after boosting, showed increased heterogeneous protective potential compared with priming with a conventional DNA vaccine (pVRC-DEC-NS3). In conclusion, a suicidal DNA vector (pSC-DEC-NS3) expressing DEC-205-targeted NS3 combined with boosting using an rAd5-based HCV vaccine (rAd5-C44P) is a good candidate for a safe and effective vaccine against HCV infection.

Protective immune responses in ducklings induced by a suicidal DNA vaccine of the sigma C gene of novel duck reovirus

A suicidal DNA vaccine based on a Semliki Forest virus (SFV) replicon was evaluated for the development of a vaccine against novel duck reovirus (NDRV). The sigma C gene of NDRV was cloned and inserted into pSCA1, an SFV DNA-based replicon vector. After transfected into BHK-21 cells, the antigenicity of the sigma C protein was confirmed using an indirect immunofluorescence and Western blot assay. Immunogenicity was studied in ducklings. The results showed that NDRV-specific antibodies, neutralizing antibodies, IFN-γ and IL-4 were well induced in ducklings. Furthermore, all of the ducklings were protected against challenge with wild-type NDRV.

Immune responses in mice vaccinated with a suicidal DNA vaccine expressing the hemagglutinin glycoprotein from the peste des petits ruminants virus

Peste des petits ruminants (PPR), an acute and highly contagious disease, affects sheep, goats, and some small ruminants. The hemagglutinin (H) glycoprotein of the PPR virus (PPRV) is considered important for inducing protective immune responses. In this study, a suicidal DNA vaccine based on the Semliki Forest virus (SFV) replicon was constructed and tested for its ability to induce immunogenicity in a mouse model. For this, the H gene of PPRV was cloned and inserted into pSCA1, an SFV replicon vector. The resultant plasmid named pSCA1-H was then transfected into BHK-21 cells following which the antigenicity of the expressed protein was confirmed by Western blotting and immunofluorescence. The pSCA1-H plasmid was then injected intramuscularly into BALB/c mice thrice at 2-week intervals. To evaluate the immunogenicity of pSCA1-H, specific antibodies and neutralizing antibodies against PPRV-H were measured using an indirect enzyme-linked immunosorbent assay and a microneutralization test, respectively. Cell-mediated immune responses were also examined using a lymphocyte proliferation assay. The results showed that pSCA1-H could express the H protein in BHK-21 cells. Specific antibodies, neutralizing antibodies, and lymphocyte proliferation responses were all induced in mice. Thus, this suicidal DNA vaccine could be a promising new approach for vaccine development against PPR.

Protective immune responses in rabbits induced by a suicidal DNA vaccine of the VP60 gene of rabbit hemorrhagic disease virus

A suicidal DNA vaccine based on a Semliki Forest virus (SFV) replicon was evaluated for the development of a vaccine against rabbit hemorrhagic disease virus (RHDV). The VP60 gene of RHDV was cloned and inserted into pSCA1, an SFV DNA-based replicon vector. The resultant plasmid, pSCA/VP60, was transfected into BHK-21 cells, and the antigenicity of the expressed protein was confirmed using indirect immunofluorescence and a western blot assay. In addition, immunogenicity was studied in rabbits. Fifteen rabbits were injected intramuscularly twice with pSCA/VP60 at 2-week intervals. They were challenged with an RHDV isolate 2weeks after the second immunization. In all cases, anti-RHDV antibodies were detected by ELISA. Additionally, the lymphocyte proliferation response was tested by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide method, and neutralizing antibodies were measured by microneutralization tests. Our results showed that RHDV-specific antibodies and an RHDV-specific cell-mediated immune response were strongly induced in rabbits. Furthermore, all of the rabbits were protected against challenge with wild type RHDV. In conclusion, we demonstrated that the suicidal DNA vaccine is a promising vaccine candidate that facilitates the prevention of rabbit hemorrhagic disease caused by RHDV.

Relevance of tumor surrounding area in chemoresistance of glioblastoma(GBM)

The mechanisms responsible for resistance to damage in normal cells might determine chemoresistance in both tumor cells and cancer stem cells (CSC). Relapse due to chemoresistant residual disease is a major cause of death in GBM. Increasing body of evidence indicates that not only tumor area (TT), but also tissue surrounding the tumor border (pTT) of GBM contains tumor cells and CSC, which could contribute to the disease progression. Therefore, the need to have a deeper insight in this area through identification of the characteristics that confer chemoresistance. In this study, the expression of molecules involved in chemoresistance was investigated in samples derived from TT and from pTT at <1 cm from the tumor border, in 40 patients with GBM. The expression of O6-methylguanine-DNA methyltransferase (MGMT), a suicidal DNA repair protein; Breast Cancer Resistance Protein (BCRP1), a drug efflux transporter, and A2B5 (c-series gangliosides) has been determined by immunohistochemistry. The percentage of MGMT positive cells was higher (p<0.0001, paired Student’s t test) in pTT (median: 53.5, range: 0.6-92.4) with respect to TT (median: 3.3, range: 0.0-70.7). The same trend was observed in BCRP1 expression (p<0.02; pTT, median: 27.6, range: 1.0-95.6; TT, median: 10.1, range: 0.2-72.1). No difference was found between pTT and TT in A2B5 expression (p=0.69, pTT, median: 29.8, range: 0.0-98.4; TT, median: 26.0, range: 0.0-96.8). Patients were then divided into two groups according to presence (group A) or absence (group B) of tumor cells in pTT. The trend previous observed in MGMT expression was maintained in both groups, while only in group A a statistically significant difference in BCRP1 expression was observed. Our results confirm that the tissue surrounding GBM is not a normal tissue, and that it represents a frontline of tumor invasion, particularly for the presence of some molecules involved in chemoresistance, which could explain the disease recurrence after the conventional treatment of GBM. Experiments about the expression of above mentioned molecules in CSC from pTT and TT are in progress. Supported by FIRB, ACCORDI DI PROGRAMMA 2010

Protective immune responses in ducklings induced by a suicidal DNA vaccine of the VP1 gene of duck hepatitis virus type 1

A suicidal DNA vaccine based on a Semliki Forest virus (SFV) replicon was evaluated for the development of a vaccine against duck hepatitis virus type 1 (DHV-1). The VP1 gene of DHV-1 was cloned and inserted into pSCA1, an SFV DNA-based replicon vector. The resultant plasmid, pSCA/VP1, was transfected into BHK-21 cells and the antigenicity of the expressed protein was confirmed using an indirect immunofluorescence and western blot assay. Immunogenicity was studied in ducklings. Ducklings were injected intramuscularly two times with pSCA/VP1 at 14 days intervals. Anti-DHV-1 antibodies were detected by ELISA, the lymphocyte proliferation response was also tested by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide method and neutralizing antibodies were measured by microneutralization tests. Our results showed that DHV-1-specific antibodies, neutralizing antibodies and lymphocyte proliferation were well induced in ducklings. Furthermore, all the ducklings were protected against challenge with wild DHV-1. In conclusion, we demonstrate that the suicidal DNA vaccine is a promising vaccine candidate facilitating the prevention of duck hepatitis caused by DHV-1.

Development of a suicidal DNA vaccine for infectious hematopoietic necrosis virus (IHNV)

We developed a suicidal DNA vaccine (pIRF1A-G-pMT-M) for salmonid fish susceptible to Infectious Hematopoietic Necrosis Virus (IHNV). The suicidal vaccine consists of two operons: i) an inducible fish promoter, the interferon regulatory factor 1A promoter (pIRF1A), driving the expression of the IHNV viral glycoprotein (G) gene that induces protection, and ii) a ZnCl 2 inducible fish promoter, the metallothionein promoter (pMT), driving the expression of the IHNV matrix (M) protein that induces apoptosis. The vaccine induces an immune response to the G protein and then induces the cell to undergo apoptosis to eliminate the DNA vaccine-containing cell. Also developed is another suicidal construct (pCMV-luc-pMT-M) for monitoring the persistence of luciferase (luc) expression after induction of apoptosis. In this study, we evaluated the inducibility of the MT promoter with ZnCl 2 and the capacity of cells transfected with the suicidal vector pCMV-luc-pMT-M to undergo apoptosis after ZnCl 2 addition. We also demonstrated the protective immunity elicited by the suicidal DNA vaccine pIRF1A-G-pMT-M, the survival of fish after treatment with ZnCl 2, and the elimination of the suicidal vector in fish after ZnCl 2 treatment.

Protective immune response in BALB/c mice induced by a suicidal DNA vaccine of the MIC3 gene of Toxoplasma gondii

To evaluate the protective efficiency of a suicidal DNA vaccine against protozoal parasite Toxoplasma gondii, the microneme protein 3 (MIC3) gene was cloned into suicidal vector pSCA1 and conventional DNA vaccine vector pcDNA3.1+ respectively, their protection against T. gondii challenge were assessed in this study. The recombinant plasmids named pSCA/MIC3 and pcDNA/MIC3 were transfected into BHK-21 cells. The expression of MIC3 in BHK-21 cells was confirmed by RT-PCR and indirect immunofluorescence test. Then BALB/c mice were immunized with pSCA/MIC3 or pcDNA/MIC3. Anti-Tg-MIC3 antibodies were detected by indirect ELISA and the cell immune response were examined by lymphocyte proliferation assay and real time RT-PCR. The results showed that the titre of anti-Tg-MIC3 antibodies, stimulation index (SI) of lymphocyte proliferation response and IFN-γ expression level induced by pSCA/MIC3 and pcDNA/MIC3 were significantly higher than controls ( P < 0.05), whereas IL-4 expression level in BALB/c mice immunized with either pSCA/MIC3 or pcDNA/MIC3 was lower than that in control group. After a lethal challenge against T. gondii, survival time of the mice immunized with this suicidal DNA vaccine pSCA/MIC3 and conventional DNA vaccine pcDNA/MIC3 were significantly prolonged in comparison with the control groups ( P < 0.05), but the difference of protective immune response in BALB/c mice between pSCA/MIC3 and pcDNA/MIC3 was not statistically significant ( P > 0.05). The findings demonstrated that like conventional DNA vaccine pcDNA/MIC3, suicidal DNA vaccine pSCA/MIC3 also provided favourable efficacy, but it could improve the biosafety of conventional vaccines. This result suggested that suicidal DNA vaccine pSCA/MIC3 is a potential candidate vaccine against toxoplasmosis.

A suicidal DNA vaccine co-expressing two major membrane-associated proteins of porcine reproductive and respiratory syndrome virus antigens induce protective responses

We constructed a suicidal DNA vaccine pSFV-ORF5m/ORF6 co-expressing GP5m (a modified GP5) and M proteins of porcine reproductive and respiratory syndrome virus (PRRSV). In mice immunization, specific immune responses were elicited by the suicidal DNA vaccine pSFV-ORF5m/ORF6. The immunogenicity and protective efficiency was then evaluated in piglets immunized with pSFV-ORF5m/ORF6 before virus challenge: PRRSV-specific neutralizing antibodies and lymphocyte proliferative responses were developed. Post-PRRSV challenge, these immune responses were further boosted and partial protection was obtained.

Rapid and prolonged stalling of human DNA topoisomerase I in UVA-irradiated genomic areas

DNA topoisomerase I appears to be involved in DNA damage and repair in a complex manner. The enzyme is required for DNA maintenance and repair, but it may also damage DNA through its covalently DNA-bound, catalytic intermediate. The latter mechanism plays a role in tumor cell killing by camptothecins, but seems also involved in oxidative cell killing and certain stages of apoptosis. Stalling and/or suicidal DNA cleavage of topoisomerase I adjacent to nicks and modified DNA bases has been demonstrated in vitro. Here, we investigate the enzyme's interactions with UVA-induced DNA lesions inside living cells. We irradiated cells expressing GFP-tagged topoisomerase I with an UVA laser focused through a confocal microscope at confined areas of the nuclei. At irradiated sites, topoisomerase I accumulated within seconds, and accumulation lasted for more than 90 min. This effect was apparently due to reduced mobility, although the enzyme was not immobilized at the irradiated nuclear sites. Similar observations were made with mutant versions of topoisomerase I lacking the active site tyrosine or the N-terminal domain, but not with the N-terminal domain alone. Thus, accumulation of topoisomerase I at UVA-modified DNA sites is most likely due to non-covalent binding to damaged DNA, and not suicidal cleavage of such lesions. The rapid onset of accumulation suggests that topoisomerase I functions in this context as a component of DNA damage recognition and/or a cofactor of fast DNA-repair processes. However, the prolonged duration of accumulation suggests that it is also involved in more long-termed processes.

Protective immune responses in guinea pigs and swine induced by a suicidal DNA vaccine of the capsid gene of swine vesicular disease virus

A suicidal DNA vaccine based on a Semliki Forest virus (SFV) replicon was evaluated for the development of a vaccine against swine vesicular disease virus (SVDV). The 1BCD gene of SVDV was cloned and inserted into pSCA1, an SFV DNA-based replicon vector. The resultant plasmid, pSCA/1BCD, was transfected into BHK-21 cells and the antigenicity of the expressed protein was confirmed using an indirect immunofluorescence assay. Immunogenicity was studied in guinea pigs and swine. Animals were injected intramuscularly three times with pSCA/1BCD at regular intervals. Anti-SVDV antibodies were detected by ELISA, the lymphocyte proliferation response was tested by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide method and neutralizing antibodies were measured by microneutralization tests. The data showed that SVDV-specific antibodies, neutralizing antibodies and lymphocyte proliferation were induced in both guinea pigs and swine. Furthermore, after three successive vaccinations with pSCA/1BCD, half of the pigs were protected against challenge with SVDV. These results should encourage further work towards the development of a DNA vaccine against SVDV.

Enhanced immunogenicity to food-and-mouth disease virus in mice vaccination with alphaviral replicon-based DNA vaccine expressing the capsid precursor polypeptide (P1)

Recently, alphavirus replicon-based DNA vaccines, also known as suicidal DNA vaccines, have emerged as an important strategy to enhance the potency of DNA vaccines. In this study, two different types of DNA vaccines encoding the capsid precursor polypeptide (P1) of foot-and-mouth disease virus (FMDV) were constructed and the immunogenicity were investigated and compared in mouse model. The first DNA vaccine, pcDP1, is a conventional plasmid DNA vaccine in which P1 was driven directly by a cytomegalovirus promoter. The second DNA vaccine, pSCAP1, is a Semliki Forest virus (SFV) replicon-based DNA vaccine encoding the same antigen. In vitro expression and characterization indicated that two vaccine vectors could correctly produce the P1 antigen. However, pSCAP1 could induce obvious apoptosis of the transfected cells. After immunization in BALB/c mice, the P1-specific ELISA antibodies, neutralizing antibodies, as well as lymphocyte proliferative responses induced by pSCAP1 were significantly higher than those obtained in mice immunized with pcDP1. Notably, mice immunized with the pSCAP1 had the determined ability of clearing virus in their sera after FMDV challenge. These results indicate that the SFV replicon-based DNA vaccine pSCAP1 are more effective than conventional DNA vaccine and it can be considered a promising approach for the development of a safety and efficacious vaccine against FMDV.

Enhancement of suicidal DNA vaccine potency by delaying suicidal DNA-induced cell death

DNA-based alphaviral RNA replicon vectors, also called suicidal DNA vectors, alleviate the concerns of integration or transformation related to conventional DNA vectors since suicidal DNA vectors eventually cause apoptosis of transfected cells. However, the expression of inserted genes in these vectors is transient and the potency of suicidal DNA vaccines may be compromised because of apoptotic cell death. Therefore, to enhance the immune response to the human papillomavirus type 16 (HPV-16) E7 antigen, we generated a DNA-based Semliki Forest virus vector, pSCA1, encoding E7 fused with BCL-xL, an antiapoptotic member of the BCL-2 family. Our results indicated that pSCA1 encoding E7/BCL-xL fusion protein delayed cell death in the pSCA1-transfected dendritic cell line and generated significantly higher E7-specific CD8(+) T-cell-mediated immune responses and better antitumor effects than pSCA1 encoding wild-type E7 gene in vaccinated mice. The antiapoptotic function of BCL-xL is important for the enhancement of antigen-specific CD8(+) T-cell responses in vaccinated mice, because a point mutant of BCL-xL lacking antiapoptotic function was ineffective. These results suggest that strategies to delay suicidal DNA-induced cell death using antiapoptotic proteins may greatly enhance the potency of suicidal DNA.

Comparison of immune responses and protective efficacy of suicidal DNA vaccine and conventional DNA vaccine encoding glycoprotein C of pseudorabies virus in mice

In the present study, the immunogenicity and protective efficacy of a suicidal DNA vaccine (pSFVC1.5) incorporating Semliki Forest virus (SFV) replicon and expressing glycoprotein C (gC) of pseudorabies virus (PrV) was investigated and compared with a conventional plasmid DNA vaccine (pcDC) encoding the same antigen. In vitro, pSFVC1.5 could express gC protein and induce apoptosis of the transfected cells. After immunization in BALB/c mice, the gC-specific ELISA antibodies and neutralizing antibodies induced by pSFVC1.5 were relatively lower than those obtained in mice immunized with pcDC. However, mice immunized with pSFVC1.5 could confer more efficient protection than pcDC (100 and 62.5%, respectively) when challenged with the field PrV at 4 weeks after secondary immunization. Further analyses of cell-mediated immune responses showed that pSFVC1.5 induced stronger lymphocyte proliferative responses and higher levels of IFN-γ, suggesting pSFVC1.5 could induce an enhanced Th1-type immune response. Collectively these results indicated that suicidal DNA vaccine is an alternative strategy to conventional DNA vaccine and can be considered a promising approach for the development of an efficacious vaccine against PrV.

707. Enhancement of Suicidal DNA Vaccine Potency by Delaying Suicidal DNA-Induced Apoptotic Cell Death

707. Enhancement of Suicidal DNA Vaccine Potency by Delaying Suicidal DNA-Induced Apoptotic Cell Death