Balb/c mice were immunized with the recombinant fusion protein gD1/313 (FpgD1/313 representing the ectodomain of HSV-1 gD), with the non-pathogenic ANGpath gE-del virus, with the plasmid pcDNA3.1-gD expressing full-length gD1 and with the recombinant immediate early (IE) HSV-1 protein ICP27. Specific antibodies against these antigens (as detected by ELISA) reached high titers with the exception of the DNA vaccine. High-grade protection against challenge with the virulent strain SC16 was found following immunization with the pcDNA3.1-gD plasmid and with the gE-del virus. Medium grade, but satisfactory protection developed after immunization with the FpgD1/313 and minimum grade protection was seen upon immunization with the IE/ICP27 polypeptide. A considerable response of peripheral blood cells (PBL) and splenocytes in the lymphocyte transformation test (LTT) was found in mice immunized with FpgD1/313, with the pcDNA3.1-gD plasmid and with the live ANGpathgE-del virus. For lymphocyte stimulation in vitro, the FpgD1/313 antigen was less effective than the purified gD1/313 polypeptide (cleaved off from the fusion protein); both proteins elicited higher proliferation at the 5 microg per 0.1 mL dose than at the 1 microg per 0.1 mL dose. The secretion of Th type 1 (TNF, IFN-gamma and IL-2) and Th type 2 (IL-4 and IL-6) cytokines was tested in the medium fluid of purified PBL and splenocyte cultures; their absolute values were expressed in relative indexes. The PBL from FpgD1/313 immunized mice showed increased secretion of both T(H)1 (TNF) as well as T(H)2 (IL-4) cytokines (7-10-fold, respectively). Splenocytes from FpgD1/313 immunized mice showed a significant (23-fold) increase in IL-4 production.

• MeSH
• aktivace lymfocytů MeSH
• buněčné linie MeSH
• cytokiny biosyntéza   imunologie   MeSH
• imunizace * MeSH
• krevní buňky imunologie   MeSH
• kultivované buňky MeSH
• lidé MeSH
• lidský herpesvirus 1 genetika   imunologie   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• protilátky virové krev   MeSH
• Simplexvirus imunologie   MeSH
• T-lymfocyty imunologie   MeSH
• vakcína proti viru herpes simplex aplikace a dávkování   imunologie   MeSH
• virové proteiny genetika   imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• cytokiny MeSH
• protilátky virové MeSH
• vakcína proti viru herpes simplex MeSH
• virové proteiny MeSH

Vaccination has remained the best method for preventing virus spread. The herpes simplex virus (HSV) candidate vaccines tested till now were mostly purified subunit vaccines and/or recombinant envelope glycoproteins (such as gB and gD). In many experiments performed in mice, guinea pigs and rabbits, clear-cut protection against acute virus challenge was demonstrated along with the reduction of the extent of latency, when established in the immunized host. The immunotherapeutic effect of herpes vaccines seems less convincing. However, introduction of new adjuvants, which shift the cytokine production of helper T-cells toward stimulation of cytotoxic T-cells (TH1 type cytokine response), reveals a promising development. Mathematical analysis proved that overall prophylactic vaccination of seronegative women, even when eliciting 40-60 % antibody response only, would reduce the frequency of genital herpes within the vaccinated population. Even when partially effective, immunotherapeutic vaccination might represent a suitable alternative of chronic chemotherapy in recurrent labial and genital herpes.

• MeSH
• adjuvancia imunologická terapeutické užití   MeSH
• atenuované vakcíny biosyntéza   imunologie   terapeutické užití   MeSH
• herpes simplex farmakoterapie   imunologie   prevence a kontrola   MeSH
• klinické zkoušky jako téma metody   MeSH
• králíci MeSH
• lidé MeSH
• lidský herpesvirus 1 imunologie   MeSH
• lidský herpesvirus 2 imunologie   MeSH
• morčata MeSH
• myši MeSH
• syntetické vakcíny biosyntéza   imunologie   terapeutické užití   MeSH
• vakcína proti viru herpes simplex biosyntéza   imunologie   terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• lidé MeSH
• morčata MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• adjuvancia imunologická MeSH
• atenuované vakcíny MeSH
• syntetické vakcíny MeSH
• vakcína proti viru herpes simplex MeSH

During the last decade, new data accumulated describing the early events during herpes simplex virus 1 (HSV-1) replication occurring before capsid formation and virion envelopment. The HSV virion carries its own specific transcription initiation factor (alpha-TIF), which functions together with other components of the cellular transcriptase complex to mediate virus-specific immediate early (IE) transcription. The virus-coded IE proteins are the transactivator and regulatory elements modulating early transcription and subsequent translation of nonstructural virus-coded proteins needed mainly for viral DNA synthesis and for the supply of corresponding nucleoside components. They also cooperate at the late transcription and translation of the virion (capsid, tegument and envelope) proteins. In addition, the transactivator IE proteins down-regulate their own transcription, while others facilitate viral mRNA processing or interfere with the presentation of newly synthesized virus antigens. Establishment of latency is closely related to the transcription of a separate category of transcripts, termed latency-associated (LAT). Formation of LATs occurs mainly in nondividing neurons which are metabolically less active and express lower levels of cellular transcription factors (nonpermissive cells). Expression of the stable non-spliced (2 kb), and especially of stable spliced (1.5 and 1.45 kb) LATs is a prerequisite for HSV reactivation. Different HSV genomes (from various HSV strains) do not undergo IE transcription at the same rate. Restricted IE transcription and the absence of viral DNA synthesis favors LAT formation and persistence of the silenced genome. Uneven levels of LAT expression and differences in the metabolic state of carrier neurons influence the reactivation competence. Under artificial or natural activation conditions, sufficient amounts of IE transactivator proteins and proteins promoting nucleoside metabolism are synthesized even in the absence of the viral alpha-TIF facilitating reactivation.

• MeSH
• aktivace viru MeSH
• genetická transkripce MeSH
• herpes simplex virus - protein Vmw65 metabolismus   MeSH
• herpes simplex virologie   MeSH
• latence viru MeSH
• lidé MeSH
• lidský herpesvirus 1 genetika   fyziologie   MeSH
• neurony metabolismus   virologie   MeSH
• proteiny bezprostředně časné metabolismus   MeSH
• trans-aktivátory metabolismus   MeSH
• transkripční faktory metabolismus   MeSH
• ubikvitinligasy MeSH
• virové proteiny metabolismus   MeSH
• virové strukturální proteiny metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• herpes simplex virus - protein Vmw65 MeSH
• herpes simplex virus type 1 protein VP22 MeSH Prohlížeč
• herpes simplex virus, type 1 protein ICP4 MeSH Prohlížeč
• ICP27 protein, human herpesvirus 1 MeSH Prohlížeč
• ICP47 protein, Herpes simplex virus MeSH Prohlížeč
• proteiny bezprostředně časné MeSH
• trans-aktivátory MeSH
• transkripční faktory MeSH
• ubikvitinligasy MeSH
• virové proteiny MeSH
• virové strukturální proteiny MeSH
• Vmw110 protein, Human herpesvirus 1 MeSH Prohlížeč