Jeff Fairman

University of Cincinnati, Cincinnati, Ohio, United States

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Publications (12)25.36 Total impact

  • Antiviral Research - ANTIVIR RES. 01/2010; 86(1).
  • Antiviral Research - ANTIVIR RES. 01/2010; 86(1).
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    ABSTRACT: Herpes simplex virus (HSV) infections are common but there is no vaccine available. We evaluated cationic liposome-DNA complexes (CLDC) as an adjuvant for an HSV gD2 vaccine and compared it to an MPL/Alum adjuvant in a guinea pig model of genital herpes. The addition of CLDC to the gD2 vaccine significantly decreased acute and recurrent disease and most importantly the number of days with recurrent virus shedding compared to gD2 alone. Reductions in these outcomes were also detected when gD2+CLDC was compared to gD2+MPL/Alum. When the vaccine and adjuvants were evaluated as therapeutic vaccines, they were ineffective. CLDC enhanced protection compared to MPL/Alum and is the first vaccine to reduce recurrent virus shedding, a key to decreasing the spread of HSV-2.
    Vaccine 10/2009; 28(21):3748-53. · 3.77 Impact Factor
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    ABSTRACT: Development of a herpes simplex virus (HSV) vaccine is a priority because these infections are common. It appears that potent adjuvants will be required to augment the immune response to subunit HSV vaccines. Therefore, we evaluated cationic liposome-DNA complexes (CLDC) as an adjuvant in a mouse model of genital herpes. Using a whole-virus vaccine (HVAC), we showed that the addition of CLDC improved antibody responses compared to vaccine alone. Most important, CLDC increased survival, reduced symptoms, and decreased vaginal virus replication compared to vaccine alone or vaccine administered with monophosphoryl lipid A (MPL) plus trehalose dicorynomycolate (TDM) following intravaginal challenge of mice. When CLDC was added to an HSV gD2 vaccine, it increased the amount of gamma interferon that was produced from splenocytes stimulated with gD2 compared to the amount produced with gD2 alone or with MPL-alum. The addition of CLDC to the gD2 vaccine also improved the outcome following vaginal HSV type 2 challenge compared to vaccine alone and was equivalent to vaccination with an MPL-alum adjuvant. CLDC appears to be a potent adjuvant for HSV vaccines and should be evaluated further.
    Clinical and vaccine Immunology: CVI 04/2009; 16(5):699-705. · 2.60 Impact Factor
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    ABSTRACT: Many new vaccines under development consist of rationally designed recombinant proteins that are relatively poor immunogens unless combined with potent adjuvants. There is only one adjuvant in common use in the U.S., aluminum phosphate or hydroxide (e.g. alum). This adjuvant, however, has significant limitations, particularly regarding the generation of strong cell-mediated (T-cell) immune responses. A novel adjuvant, JVRS-100, composed of cationic liposome-DNA complexes (CLDC) has been evaluated for immune enhancing activity. The JVRS-100 adjuvant has been shown to elicit robust immune responses compared to CpG oligonucleotides, alum, and MPL adjuvants, and efficiently enhances both humoral and cellular immune responses. Safety has been evaluated in preclinical studies, and the adjuvant is now in early-stage clinical development. One application of this novel adjuvant is to augment the immune responses to recombinant subunit antigens, which are often poorly immunogenic. The JVRS-100 adjuvant, when combined with a recombinant influenza hemagglutinin (H1), elicited increased specific antibody and T-cell responses in mice. Single-dose vaccination and prime/boost vaccinations with JVRS-100-H1 were both shown to be protective (i.e., survival, reduced weight loss) following H1N1 (PR/8/34) virus challenge. Enhanced immunological responses could be critically important for improved efficacy and dose-sparing of a recombinant influenza vaccine.
    Biologicals 04/2009; 37(3):141-7. · 1.62 Impact Factor
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    ABSTRACT: Cationic liposome–DNA complexes (CLDC) are cationic/neutral lipid carriers complexed with plasmid DNA that when administered systemically results in a robust TH1 cytokine response. CLDC have been shown to be effective in prophylaxis and therapeutic treatment of animal models of viral disease. To determine the contribution of liposomal delivery and CpG content of the plasmid DNA to the efficacy of CLDC; plasmid, CpG-free plasmid DNA, or CpG-containing oligodeoxynucleotides (ODN) with and without liposomes, as well as poly(I:C12U), were evaluated for their ability to elicit protection against lethal Punta Toro virus (PTV, Bunyaviridae, phlebovirus) challenge in hamsters. CLDC-containing plasmid significantly improved survival, decreased systemic and liver viral loads, and reduced liver damage due to progression of viral infection. Mouse-reactive ODNs complexed with liposomes failed to protect hamsters, whereas ODNs known to cross-react with human and mouse (CpG 2006) or non-liposomal poly(I:C12U) showed survival benefit but did not limit liver injury. Liposomes complexed with a non-CpG motif-containing plasmid reduced liver viral load and tissue damage, but did not protect hamsters from death. To evaluate the mechanisms of the enhanced activity of CLDC, microarray experiments examined differences in the gene expression profile. The results suggest a broad TH1 response elicited by liposomal delivery of a diverse sequence containing CpG and non-CpG elements may be a more effective antiviral treatment than other nucleic acid based immunotherapeutics.
    Antiviral research 01/2009; · 3.61 Impact Factor
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    ABSTRACT: Previous studies have demonstrated that systemically administered immunotherapy can protect mice from systemic challenge with the bacterial pathogen Francisella tularensis. However, for protection from inhalational challenge with this bacterium, we wondered if mucosally administered immunotherapy might be more effective. Therefore, we administered cationic liposome–DNA complexes (CLDC), which are potent activators of innate immunity, intranasally (i.n.) and assessed the effectiveness of protection from lethal inhalational challenge with F. tularensis. We found that pretreatment by i.n. administration of CLDC 24 h prior to bacterial challenge elicited nearly complete protection of BALB/c mice from lethal challenge with F. tularensis LVS strain. We also observed that mucosal CLDC immunotherapy provided a statistically significant increase in survival time in mice challenged with the highly virulent F. tularensis Schu4 strain. Protection was associated with a significant reduction in bacterial burden in the lungs, liver, and spleen. Mucosal administration of CLDC elicited significantly increased expression of IL-12, IFN-γ, TNF-α, IFN-β and IFN-α genes in the lung as detected by real-time quantitative PCR. In vitro treatment of F. tularensis infected macrophages with CLDC-elicited cytokines also significantly suppressed intracellular replication of F. tularensis in infected macrophages. In vivo, depletion of NK cells prior to administration of CLDC completely abolished the protective effects of CLDC immunotherapy. CLDC-elicited protection was also dependent on induction of IFN-γ production in vivo. We conclude therefore that activation of local pulmonary innate immune responses is capable of eliciting significant protection from inhalational exposure to a virulent bacterial pathogen.
    Vaccine 01/2009; · 3.77 Impact Factor
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    ABSTRACT: This pilot study tested the immunogenicity of a novel cationic liposome-DNA complex (CLDC) immunomodulatory vaccine adjuvant. Combined with a specific antigen, CLDC enhanced anti-SIV immune responses induced by various SIV vaccine candidates. Rhesus macaques immunized in the presence of CLDC developed stronger SIV-specific T and B cell responses compared to animals immunized without CLDC. These differences persisted and resulted in better memory responses after an in vivo boost of the animals several months later with whole AT-2 inactivated SIVmac239. Thus, CLDC should be explored further as a potential immunomodulatory adjuvant in HIV vaccine design.
    Human vaccines 08/2008; 5(3):141-50. · 3.14 Impact Factor
  • Antiviral Research - ANTIVIR RES. 01/2007; 74(3).
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    ABSTRACT: Intravenous gene delivery using liposome-DNA complexes (LDC) has previously been shown to elicit antitumor activity, but only in rodent tumor models. Therefore, we conducted a study to determine in a large animal spontaneous tumor model whether intravenous infusions of LDC could target gene expression to cutaneous tumor tissues and whether repeated treatments had an effect on tumor growth or angiogenesis. A total of 13 dogs with cutaneous soft tissue sarcomas were enrolled in the study and were randomized to receive a series of 6 weekly infusions of LDC containing either canine endostatin DNA or DNA encoding an irrelevant gene (luciferase). Serial tumor biopsies were obtained to assess transgene expression, tumor microvessel density (MVD), and intratumoral leukocyte inflammatory responses. We found that intravenous infusion of LDC did not result in detectable gene expression in cutaneous tumor tissues. However, two of 13 treated dogs had objective tumor responses and eight dogs had stable disease during the treatment period. In addition, a significant decrease in tumor MVD was noted in six of 12 treated dogs at the completion of six treatments. These results suggest that intravenous infusions of LDC may elicit nonspecific antitumor activity and inhibit tumor angiogenesis.
    Cancer Gene Therapy 04/2006; 13(3):306-17. · 2.95 Impact Factor
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    ABSTRACT: Cationic liposome-DNA complexes (CLDC) have been demonstrated to induce potent antitumor activities. The ability of these complexes to elicit protective immunity against viral infections has not been fully explored. Here we report findings on the use of CLDC as an antiviral agent in a mouse model of acute phleboviral (Punta Toro virus) disease. CLDC treatment of mice challenged with Punta Toro virus (PTV) resulted in dramatic increases in survival and reduced viral burden and other parameters indicative of protection against disease. CLDC were effective when administered by intraperitoneal and intravenous routes and elicited protective immunity when given within 1 day of virus challenge. Treatments administered 36 h or longer after challenge, however, were not effective in preventing mortality or disease. CLDC treatment induced release of a number of potential antiviral cytokines including IFN-gamma, IL-12, and IFN-alpha. Taken together, our findings indicate that non-specific immunotherapy with CLDC appears to be an effective treatment for blocking PTV-induced disease and suggests that further exploration in other viral disease models may be warranted.
    Antiviral Research 04/2006; 69(3):165-72. · 3.93 Impact Factor
  • ADVS Faculty Publications. 01/2006;