phytochemical screening, antibacterial, antifungal, antiviral, cytotoxic, and anti-quorum-sensing properties of teucrium polium l. aerial parts methanolic extract.the chemical profile of teucrium polium l. (t. polium) methanolic extract was tested using liquid chromatography coupled with high resolution mass spectrometry (hr-lcms). disc diffusion and microdilution assays were used for the antimicrobial activities. coxsackievirus b-3 (cvb3) and herpes simplex virus type 2 (hsv-2) were used for the antiviral activities. chromobacterium violaceum (atcc 12472 and cv026) and pseudomonas aeruginosa pao1 were used as starter strains for the anti-quorum sensing t ...202033114026
preclinical safety evaluation of oncolytic herpes simplex virus type 2.oncolytic virotherapy is a new and safe therapeutic strategy based on the inherent cytotoxicity of oncolytic viruses and their ability to replicate and spread within tumors in a selective manner. in a previous study, a new type of oncolytic herpes simplex virus type 2 (ohsv-2, named oh2) was constructed to treat human cancers. that study demonstrated that oh2 is genetically and biologically stable. its antitumor activity was maintained, even after passaging the virus for >20 generations. to adva ...201930499341
vaccine-mediated inhibition of the transporter associated with antigen processing is insufficient to induce major histocompatibility complex e-restricted cd8+ t cells in nonhuman primates.major histocompatibility complex e (mhc-e) is a highly conserved nonclassical mhc-ib molecule that tightly binds peptides derived from leader sequences of classical mhc-ia molecules for presentation to natural killer cells. however, mhc-e also binds diverse foreign and neoplastic self-peptide antigens for presentation to cd8+ t cells. although the determinants of mhc-e-restricted t cell priming remain unknown, these cells are induced in humans infected with pathogens containing genes that inhibi ...201931315990
acute infection and subsequent subclinical reactivation of herpes simplex virus 2 after vaginal inoculation of rhesus macaques.herpes simplex virus 2 (hsv-2) is a common sexually transmitted infection with a highly variable clinical course. many infections quickly become subclinical, with episodes of spontaneous virus reactivation. to study host-hsv-2 interactions, an animal model of subclinical hsv-2 infection is needed. in an effort to develop a relevant model, rhesus macaques (rm) were inoculated intravaginally with two or three hsv-2 strains (186, 333, and/or g) at a total dose of 1 × 107 pfu of hsv-2 per animal. in ...201930333177
griffithsin carrageenan fast dissolving inserts prevent shiv hsv-2 and hpv infections in vivo.human immunodeficiency virus (hiv) pre-exposure prophylaxis (prep) strategies with proven in vivo efficacy rely on antiretroviral drugs, creating the potential for drug resistance and complicated treatment options in individuals who become infected. moreover, on-demand products are currently missing from the prep development portfolio. griffithsin (grft) is a non-antiretroviral hiv entry inhibitor derived from red algae with an excellent safety profile and potent activity in vitro. when combined ...201830250170
a trivalent gc2/gd2/ge2 vaccine for herpes simplex virus generates antibody responses that block immune evasion domains on gc2 better than natural infection.vaccines for prevention and treatment of genital herpes are high public health priorities. our approach towards vaccine development is to focus on blocking virus entry mediated by herpes simplex virus type 2 (hsv-2) glycoprotein d (gd2) and to prevent the virus from evading complement and antibody attack by blocking the immune evasion domains on hsv-2 glycoproteins c (gc2) and e (ge2), respectively. hsv-2 gc2 and ge2 are expressed on the virion envelope and infected cell surface where they are p ...201930551986
increased frequency of virus shedding by herpes simplex virus 2-infected guinea pigs in the absence of cd4+ t lymphocytes.reactivation of herpes simplex virus 2 (hsv-2) results in infection of epithelial cells at the neuro-epithelial junction and shedding of virus at the epithelial surface. virus shedding can occur in either the presence or absence of clinical disease and is usually of short duration, although the shedding frequency varies among individuals. the basis for host control of virus shedding is not well understood, although adaptive immune mechanisms are thought to play a central role. to determine the i ...201930463981
vaccine-induced antibodies to herpes simplex virus glycoprotein d epitopes involved in virus entry and cell-to-cell spread correlate with protection against genital disease in guinea pigs.herpes simplex virus type 2 (hsv-2) glycoprotein d (gd2) subunit antigen is included in many preclinical candidate vaccines. the rationale for including gd2 is to produce antibodies that block crucial gd2 epitopes involved in virus entry and cell-to-cell spread. hsv-2 gd2 was the only antigen in the herpevac trial for women that protected against hsv-1 genital infection but not hsv-2. in that trial, a correlation was detected between gd2 elisa titers and protection against hsv-1, supporting the ...201829791513
expression of recombinant herpes simplex virus type 2 glycoprotein d by high-density cell culture of spodoptera frugiperda.herpes simplex virus type 2 (hsv-2) is the major cause of genital herpes in humans. the glycoprotein d of hsv-2 (gd2) is a promising subunit vaccine candidate for the treatment of genital herpes. the aim of the present study was to express a biologically active recombinant gd2 in eukaryotic baculovirus system in quantities sufficient for further studies. human cdna encoding a gd2 protein with 393 amino acids was subcloned into the pfastbac htb vector and the recombinant protein was expressed in ...201232214412
protection against herpes simplex virus type 2 infection in a neonatal murine model using a trivalent nucleoside-modified mrna in lipid nanoparticle vaccine.neonatal herpes is a dreaded complication of genital herpes infection in pregnancy. we recently compared two vaccine platforms for preventing genital herpes in female mice and guinea pigs and determined that hsv-2 glycoproteins c, d and e expressed using nucleoside-modified mrna in lipid nanoparticles provided better protection than the same antigens produced as baculovirus proteins and administered with cpg and alum. here we evaluated mrna and protein immunization for protection against neonata ...202033041105
herpes simplex virus type 2 trivalent protein vaccine containing glycoproteins c, d and e protects guinea pigs against hsv-1 genital infection.a vaccine to prevent genital herpes is an unmet public health need. we previously reported that a trivalent vaccine containing herpes simplex virus type 2 (hsv-2) glycoproteins c, d, and e (gc2, gd2, ge2) produced in baculovirus and administered with cpg/alum as adjuvants blocks immune evasion mediated by gc2 and ge2 and virus entry by gd2. the vaccine protected guinea pigs against hsv-2 vaginal infection. we evaluated whether the hsv-2 vaccine cross-protects against hsv-1 because many first-tim ...202032347775
a vaccine containing highly purified virus particles in adjuvant provides high level protection against genital infection and disease in guinea pigs challenged intravaginally with homologous and heterologous strains of herpes simplex virus type 2.infection with herpes simplex viruses (hsvs) represents a significant health burden worldwide with hsv-1 and hsv-2 causing genital disease and hsv-2 contributing to human immunodeficiency virus acquisition. despite great need, there is currently no licensed vaccine against hsv. in this report, we evaluated the protective efficacy of a vaccine containing highly purified, inactivated hsv-2 particles (with and without additional recombinant glycoprotein d) formulated with a monophosphoryl lipid a/a ...202031611098
nucleoside-modified mrna encoding hsv-2 glycoproteins c, d, and e prevents clinical and subclinical genital herpes.the goals of a genital herpes vaccine are to prevent painful genital lesions and reduce or eliminate subclinical infection that risks transmission to partners and newborns. we evaluated a trivalent glycoprotein vaccine containing herpes simplex virus type 2 (hsv-2) entry molecule glycoprotein d (gd2) and two immune evasion molecules: glycoprotein c (gc2), which binds complement c3b, and glycoprotein e (ge2), which blocks immunoglobulin g (igg) fc activities. the trivalent vaccine was administere ...201931541030
intranasal nanoemulsion-adjuvanted hsv-2 subunit vaccine is effective as a prophylactic and therapeutic vaccine using the guinea pig model of genital herpes.genital herpes is a sexually transmitted disease representing a major global health concern. currently, there is no approved vaccine and existing antiviral therapies exhibit limited efficacy. herein, we describe an intranasal (in) vaccine comprised of hsv-2 surface glycoproteins gd2 and gb2 formulated in a nanoemulsion adjuvant (ne01-gd2/gb2). using the hsv-2 genital herpes guinea pig model, we demonstrate that in ne01-gd2/gb2 induces higher levels of neutralizing antibody compared to a monovale ...201931515143
successful application of prime and pull strategy for a therapeutic hsv promising approach for a herpes simplex virus vaccine uses a vaccine to prime and a chemoattractant to pull immune cells into the genital tract. we evaluated subunit vaccines (prime) and imiquimod (pull) in the guinea pig (gp) model of recurrent herpes simplex virus type-2 (hsv-2). following vaginal hsv-2 infection, gps were vaccinated with various combination of glycoproteins and adjuvant with or without subcutaneous or local applications of imiquimod after infection. animals were examined ...201931396405
herpes simplex virus 2 in autonomic ganglia: evidence for spontaneous reactivation.herpes simplex virus 2 (hsv-2) can be transmitted in the presence or absence of lesions, allowing efficient spread among the general population. recurrent hsv genital lesions are thought to arise from reactivated latent virus in sensory cell bodies of the dorsal root ganglia (drg). however, hsv-2 has also been found latent in autonomic ganglia. spontaneous reactivation or a low level of chronic infection could theoretically also occur in these peripheral nervous tissues, contributing to the pres ...201930894469
therapeutic mucosal vaccination of herpes simplex virus 2-infected guinea pigs with ribonucleotide reductase 2 (rr2) protein boosts antiviral neutralizing antibodies and local tissue-resident cd4+ and cd8+ trm cells associated with protection against recurrent genital herpes.reactivation of herpes simplex virus 2 (hsv-2) from latency causes viral shedding that develops into recurrent genital lesions. the immune mechanisms of protection against recurrent genital herpes remain to be fully elucidated. in this preclinical study, we investigated the protective therapeutic efficacy, in the guinea pig model of recurrent genital herpes, of subunit vaccine candidates that were based on eight recombinantly expressed hsv-2 envelope and tegument proteins. these viral protein an ...201930787156
development of disease and immunity at the genital epithelium following intrarectal inoculation of male guinea pigs with herpes simplex virus type 2.most analyses of genital immunity to herpes simplex virus type 2 (hsv-2) have been performed in females, consequently immune protection of the male genital epithelium is incompletely understood. we developed a model of male genital hsv-2 infection resulting from intrarectal inoculation of guinea pigs. vesicular lesions developed transiently on the perineum and foreskin concurrent with acute virus shedding. virus shedding and recurrent genital lesions were also detected after establishment of a l ...201930412859
herpes simplex virus 2 latency-associated transcript (lat) region mutations do not identify a role for lat-associated micrornas in viral reactivation in guinea pig genital models.despite the long-standing observation that herpes simplex virus (hsv) latency-associated transcript (lat) promoter deletion viruses show impaired recurrence phenotypes in relevant animal models, the mechanism by which these sequences exert this phenotypic effect is unknown. we constructed and evaluated four mutant hsv-2 isolates with targeted mutations in the lat promoter and lat-associated micrornas (mirnas) affecting (i) the lat tata box; (ii) the lat icp4-binding site; (iii) mirna i (mir-i) a ...201829720520
assessment of two novel live-attenuated vaccine candidates for herpes simplex virus 2 (hsv-2) in guinea pigs.treatment to ameliorate the symptoms of infection with herpes simplex virus 2 (hsv-2) and to suppress reactivation has been available for decades. however, a safe and effective preventative or therapeutic vaccine has eluded development. two novel live-attenuated hsv-2 vaccine candidates (rvx201 and rvx202) have been tested preclinically for safety. hartley guinea pigs were inoculated vaginally (n = 3) or intradermally (n = 16) with either vaccine candidate (2 × 107 pfu) and observed for disease ...202133805768
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