Biomedical subjects

R L Arnold

Publications and source records attributed to R L Arnold.

10 recordsLinked to original sources

PubMed2000

Plasmid DNA-expressed secreted and nonsecreted forms of herpes simplex virus glycoprotein D2 induce different types of immune responses.

Herpes simplex viruses (HSVs) are significant pathogens and major targets of vaccine development. Several attempts have been made to develop prophylactic and therapeutic vaccines for HSV types 1 and 2. Although these vaccines elicit strong humoral responses, the overall impact on pathology has been disappointing. An effective vaccine for HSV must induce both humoral and cellular immune responses. DNA vaccines are ideal candidates for HSV vaccines because they induce both types of immune responses. This study showed that the type of immune response generated by immunization with DNA vaccines is modulated by expression of various forms of an antigen, each with a different cellular localization. Expression of cell-associated forms of HSV-2 glycoprotein D (gD) induces primarily a Th1 response, whereas expression of secreted gD results in a Th2 response. Immunization with plasmids expressing different forms of the antigen may increase the efficacy of a vaccine.

Animals↗

PubMed2000

Herpes simplex virus DNA vaccine efficacy: effect of glycoprotein D plasmid constructs.

The impact of vaccination with plasmid DNA encoding full-length glycoprotein D (gD) from herpes simplex virus (HSV) type 2 (gD2), secreted gD2, or cytosolic gD2 was evaluated in mice and guinea pigs. Immunization with plasmids encoding full-length gD2 or secreted gD2 produced high antibody levels, whereas immunization with DNA encoding cytosolic gD2 resulted in significantly lower antibody titers in both species (P<.001). Vaccination with DNA encoding full-length or secreted gD2 significantly reduced acute disease in mice and guinea pigs (both P<.001) and subsequent recurrent disease in guinea pigs (P<.05). In guinea pigs, immunization with DNA encoding cytosolic gD2 did not protect from acute or recurrent disease, whereas in mice it did protect, but not as well as DNA encoding full-length or secreted gD2. None of the vaccines resulted in improved virus clearance from the inoculation site, and none significantly reduced recurrent disease when used as a therapeutic vaccine in HSV-2-infected guinea pigs.

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PubMed1999

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. Following intravaginal HSV-2 challenge, vaginal viral replication was reduced in both models with peak reductions of greater than 99%. Immunization also decreased the number of animals developing any clinical disease (p < 0.001) and the severity of the acute disease (total lesion score 6.4 versus 0.6 in guinea pigs, p < 0.001). Further recurrent lesion days were reduced from 14.5 to 4.9 days in immunized guinea pigs (p < 0.001). DNA immunization with gD2 + bupivacaine was effective in reducing clinical disease and viral replication in both guinea pigs and mice.

Animals↗

PubMed1999

IL-12 gene as a DNA vaccine adjuvant in a herpes mouse model: IL-12 enhances Th1-type CD4+ T cell-mediated protective immunity against herpes simplex virus-2 challenge.

IL-12 has been shown to enhance cellular immunity in vitro and in vivo. Recent reports have suggested that combining DNA vaccine approach with immune stimulatory molecules delivered as genes may significantly enhance Ag-specific immune responses in vivo. In particular, IL-12 molecules could constitute an important addition to a herpes vaccine by amplifying specific immune responses. Here we investigate the utility of IL-12 cDNA as an adjuvant for a herpes simplex virus-2 (HSV-2) DNA vaccine in a mouse challenge model. Direct i.m. injection of IL-12 cDNA induced activation of resting immune cells in vivo. Furthermore, coinjection with IL-12 cDNA and gD DNA vaccine inhibited both systemic gD-specific Ab and local Ab levels compared with gD plasmid vaccination alone. In contrast, Th cell proliferative responses and secretion of cytokines (IL-2 and IFN-gamma) and chemokines (RANTES and macrophage inflammatory protein-1alpha) were significantly increased by IL-12 coinjection. However, the production of cytokines (IL-4 and IL-10) and chemokine (MCP-1) was inhibited by IL-12 coinjection. IL-12 coinjection with a gD DNA vaccine showed significantly better protection from lethal HSV-2 challenge compared with gD DNA vaccination alone in both inbred and outbred mice. This enhanced protection appears to be mediated by CD4+ T cells, as determined by in vivo CD4+ T cell deletion. Thus, IL-12 cDNA as a DNA vaccine adjuvant drives Ag-specific Th1 type CD4+ T cell responses that result in reduced HSV-2-derived morbidity as well as mortality.

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PubMed1974