Genetic resistance to clinical mousepox (ectromelia virus) varies among inbred laboratory mice and is

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Across the addictions field, the primary outcome in treatment research has been reduction in drug consumption. A comprehensive view of the impact of substance use disorders on human functioning suggests that effective treatments should address the many consequences and features of addiction beyond drug use, a recommendation forwarded by multiple expert panels and review articles. Despite recurring proposals, and a compelling general rationale for moving beyond drug use as the sole standard for evaluating addiction treatment, the field has yet to adopt any core set of “other” measures that are routinely incorporated into treatment research. Among the many reasons for the limited impact of previous proposals has been the absence of a clear set of guidelines for selecting candidate outcomes. This paper is the result of the deliberations of a panel of substance abuse treatment and research experts convened by the National Institute on Drug Abuse to discuss appropriate outcome measures for clinical trials of substance abuse treatments. This paper provides an overview of previous recommendations and outlines specific guidelines for consideration of candidate outcomes. A list of outcomes meeting those guidelines is described and illustrated in detail with two outcomes: craving and quality of life. The paper concludes with specific recommendations for moving beyond the outcome listing offered in this paper to promote the programmatic incorporation of these outcomes into treatment research.

Lyashchenko, K.P.; Greenwald, R.; Esfandiari, J.; Chambers, M.A.; Vicente, J.; Gortazar, C.; Santos, N.; Correia-Neves, M.; Buddle, B.M.; Jackson, R.; O'Brien, D.J.; Schmitt, S.; Palmer, M. V.; Delahay, R.J.; and Waters, W.R., "Animal-side serologic assay for rapid detection of Mycobacterium Bovis infection in multiple species of free-ranging wildlife" (2008 AbstractNumerous species of mammals are susceptible to Mycobacterium bovis, the causative agent of bovine tuberculosis (TB). Several wildlife hosts have emerged as reservoirs of M. bovis infection for domestic livestock in different countries. In the present study, blood samples were collected from Eurasian badgers (n = 1532), white-tailed deer (n = 463), brushtail possums (n = 129), and wild boar (n = 177) for evaluation of antibody responses to M. bovis infection by a lateral-flow rapid test (RT) and multiantigen print immunoassay (MAPIA). Magnitude of the antibody responses and antigen recognition patterns varied among the animals as determined by MAPIA; however, MPB83 was the most commonly recognized antigen for each host studied. Other seroreactive antigens included ESAT-6, CFP10, and MPB70. The agreement of the RT with culture results varied from 74% for possums to 81% for badgers to 90% for wild boar to 97% for white-tailed deer. Small numbers of wild boar and deer exposed to M. avium infection or paratuberculosis, respectively, did not cross-react in the RT, supporting the high specificity of the assay. In deer, whole blood samples reacted similarly to corresponding serum specimens (97% concordance), demonstrating the potential for field application. As previously demonstrated for badgers and deer, antibody responses to M. bovis infection in wild boar were positively associated with advanced disease. Together, these findings suggest that a rapid TB assay such as the RT This article is a U.S. government work, and is not subject to copyright in the United States.may provide a useful screening tool for certain wildlife species that may be implicated in the maintenance and transmission of M. bovis infection to domestic livestock. #

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Population control has become a major problem in many wildlife species. Fertility control through immunocontraception has been proposed as a method for reducing population size. We have tested the concept that immunocontraception can be achieved with a recombinant ectromelia virus expressing an ovary-specific antigen, the mouse zona pellucida 3 (ZP3) glycoprotein. Female mice infected with the recombinant virus produced autoimmune antibodies against ZP3 and were infertile for 5-9 mo after infection. For almost half the infertile mice, immunity to ZP3 was associated with a disruption of ovarian follicular development and the depletion of mature follicles without observable oophoritis. Mice returned to fertility as the anti-ZP3 antibody level in the serum decreased. Reinfection of the mice with the recombinant virus boosted the anti-ZP3 response and restored infertility.

We have established that mucosal immunization can generate high-avidity human immunodeficiency virus (HIV)-specific CD8(+) T cells compared with systemic immunization, and interleukin (IL)-13 is detrimental to the functional avidity of these T cells. We have now constructed two unique recombinant HIV-1 vaccines that co-express soluble or membrane-bound forms of the IL-13 receptor α2 (IL-13Rα2), which can "transiently" block IL-13 activity at the vaccination site causing wild-type animals to behave similar to an IL-13 KO animal. Following intranasal/intramuscular prime-boost immunization, these IL-13Rα2-adjuvanted vaccines have shown to induce (i) enhanced HIV-specific CD8(+) T cells with higher functional avidity, with broader cytokine/chemokine profiles and greater protective immunity using a surrogate mucosal HIV-1 challenge, and also (ii) excellent multifunctional mucosal CD8(+) T-cell responses, in the lung, genito-rectal nodes (GN), and Peyer's patch (PP). Data revealed that intranasal delivery of these IL-13Rα2-adjuvanted HIV vaccines recruited large numbers of unique antigen-presenting cell subsets to the lung mucosae, ultimately promoting the induction of high-avidity CD8(+) T cells. We believe our novel IL-13R cytokine trap vaccine strategy offers great promise for not only HIV-1, but also as a platform technology against range of chronic infections that require strong sustained high-avidity mucosal/systemic immunity for protection.

A strong cell-mediated immune response is critical for controlling viral infections and is regulated by a number of cytokines, including IL-12 and IL-18. Indeed, some viruses have evolved to specifically target these pathways to counter the host immune response. Orthopoxviruses, including ectromelia virus, encode immune evasion molecules that specifically target IL-18 and IFN-γ. We hypothesized that IL-12 and IL-18 are pivotal for induction of IFN-γ production and subsequent generation of an effective host response to ectromelia virus infection. In this study, we demonstrate that absence of both IL-12p40 and IL-18 resulted in increased susceptibility to infection that was associated with skewing of the cytokine response to Th2 and a reduction in NK and CTL responses. The decrease in CTL response correlated with a defect in CD8+ T cell proliferation and lower numbers of virus-specific CD8+ T cells. Lack of either IL-12p40 and/or IL-18 was also associated with reduced numbers of CD8+ T cells at sites of infection and with an increase in the numbers of splenic T regulatory cells. Taken together, our data indicate that IL-12p40 and IL-18 act in concert and play an important antiviral role through the up-regulation of IFN-γ production and cell-mediated immune responses.