Novel inactivation of the causative fungal pathogen of white-nose syndrome with methoxsalen plus ultraviolet A or B radiation.

White-nose syndrome is a fungal disease responsible for the rapid decline of North American bat populations. This study addressed a novel method for inactivating Pseudogymnoascus destructans, the causative agent of WNS, using ultraviolet A (UVA) or B (UVB) radiation in combination with methoxsalen, a photosensitizer from the furanocoumarin family of compounds. Fungal spore suspensions were diluted in micromolar concentrations of methoxsalen (50-500 μM), then exposed to fixed doses of UVA radiation (500-5000 mJ/cm2), followed by plating on germination media.

Gravity Probe B: final results of a space experiment to test general relativity.

Gravity Probe B, launched 20 April 2004, is a space experiment testing two fundamental predictions of Einstein's theory of general relativity (GR), the geodetic and frame-dragging effects, by means of cryogenic gyroscopes in Earth orbit. Data collection started 28 August 2004 and ended 14 August 2005. Analysis of the data from all four gyroscopes results in a geodetic drift rate of -6601.

Epitope mapping of full-length glycoprotein D from HSV-2 reveals a novel CD4+ CTL epitope located at the transmembrane-cytoplasmic junction.

The glycoprotein D of HSV-2 (gD2) is currently a leading candidate vaccine target for genital herpes vaccines as both cellular and humoral responses can be generated against it. However, little is known about how vaccine composition will affect T cell epitope selection. A panel of 15-mer peptides (with 11 amino acid overlap) spanning full-length gD2 was used to investigate the fine specificity of T cell responses to gD2 as well as the role of vaccine composition on epitope selection.

Interleukin-12 redirects murine immune responses to soluble or aluminum phosphate adsorbed HSV-2 glycoprotein D towards Th1 and CD4+ CTL responses.

The type of immune response elicited against HSV-2 infection may be a factor in the frequency and severity of recurrent disease, with non-recurrent status being associated with a Th1-like response. As administration of glycoprotein D subunit formulated with an aluminum-based adjuvant induces predominantly Th2-like immune responses, we sought to assess the ability of IL-12 to redirect anti-HSV immunity towards a Th1 response. Co-administration of gD with IL-12 resulted in gD-specific antibody subclass switching from predominantly IgG1 observed in mice immunized with either gD or gD/AlPO4 to a more balanced combination of IgG1 and IgG2a, and enhanced virus neutralizing activity.

Immunity induced by DNA immunization with herpes simplex virus type 2 glycoproteins B and C.

The complete sequence of herpes simplex virus type 2 (HSV-2) glycoproteins B and C (gB & gC) were cloned into plasmid expression vectors and evaluated in murine and guinea pig genital HSV-2 models. Balb/c mice were immunized with either pgB-2 or pgC-2 plasmids intramuscularly (IM) or intradermally (ID). The vaccines induced HSV-2-specific neutralizing and ELISA IgG antibody, but little or no enhancement of viral clearance from the vagina was detected following intravaginal challenge.

Effects of DNA immunization formulated with bupivacaine in murine and guinea pig models of genital herpes simplex virus infection.

The immunogenicity and efficacy of a herpes simplex virus type 2 glycoprotein D (gD2) DNA vaccine formulated with bupivacaine was evaluated using murine and guinea pig models of genital herpes. Animals received three doses of 100 microg of gD2 plasmid or control plasmid intramuscularly prior to intravaginal challenge with HSV-2. Immunization induced HSV ELISA and neutralizing antibody in serum and ELISA antibody in the vaginal secretions of all animals evaluated.

Antiviral activity of herpes simplex virus vectors expressing murine alpha 1-interferon.

Mutant herpes simplex virus type I (HSV-1) vectors were engineered to express murine alpha 1 interferon (IFN) and assessed for their ability to inhibit the replication of challenge viruses in infection of monolayer cell cultures. The alpha 1 IFN gene was placed under control of the Rous sarcoma virus (RSV) long terminal repeat (LTR) region in the thymidine kinase (tk) locus of both the wild-type HSV-1 strain KOS and the replication-defective KOS mutant dl20, in which both copies of the ICP4 immediate-early (IE) gene are deleted. To evaluate IFN expression, vector-infected cell culture media from epithelial, fibroblast and neuronal cells were assayed for alpha IFN release.

The mouse model and understanding immunity to herpes simplex virus.

Investigation of the immune response to herpes simplex virus (HSV) has progressed rapidly, mainly through the use of various animal models of human disease. Murine models of HSV infection have been explored extensively and have yielded a wide array of insights into the mechanisms of antiviral immunity. Current research has focused on defining the role of individual viral envelope glycoproteins in stimulating a protective B and T cell response, with the ultimate goal of identifying the minimum effective immunization unit.

Protection against zosteriform spread of herpes simplex virus by monoclonal antibodies.

The in vivo protective role of herpes simplex virus (HSV-1)-specific antibody was analyzed using monoclonal antibodies (MAbs) reactive with discrete antigenic sites on glycoproteins B, C, and D (gB, gC, gD) in the murine zosteriform spread model of HSV-1. All of the anti-gC and anti-gD MAbs, and one of four anti-gB MAbs (B6) were protective. The in vitro abilities of the MAbs to neutralize HSV-1 and mediate antibody-dependent cellular cytotoxicity (ADCC) against HSV-1-infected cells were examined as potential mechanistic correlates to in vivo protection.

Herpes simplex virus type 1-specific immunity induced by peptides corresponding to an antigenic site of glycoprotein B.

Herpes simplex virus (HSV) envelope glycoproteins are the prime targets of adaptive antiviral immunity. Previous investigation identified a protective, neutralizing, glycoprotein B1 (gB-1)-reactive monoclonal antibody (MAb B6) and localized the linear epitope recognized by the MAb to residue 84 of gB-1. Three overlapping peptides (two 20-mers and one 18-mer), together spanning amino acids 63 to 110 of the wild-type sequence of gB-1, were synthesized and analyzed for their ability to stimulate immunity which cross-reacts with HSV-1.