Protective T cell immunity in mice following protein-TLR7/8 agonist-conjugate immunization requires aggregation, type I IFN, and multiple DC subsets

The success of a non-live vaccine requires improved formulation and adjuvant selection to generate robust T cell immunity following immunization. Here, using protein linked to a TLR7/8 agonist (conjugate vaccine), we investigated the functional properties of vaccine formulation, the cytokines, and the DC subsets required to induce protective multifunctional T cell immunity in vivo. The conjugate vaccine required aggregation of the protein to elicit potent Th1 CD4(+) and CD8(+) T cell responses. Remarkably, the conjugate vaccine, through aggregation of the protein and activation of TLR7 in vivo, led to an influx of migratory DCs to the LN and increased antigen uptake by several resident and migratory DC subsets, with the latter effect strongly influenced by vaccine-induced type I IFN. Ex vivo migratory CD8(-)DEC205(+)CD103(-)CD326(-) langerin-negative dermal DCs were as potent in cross-presenting antigen to naive CD8(+) T cells as CD11c(+)CD8(+) DCs. Moreover, these cells also influenced Th1 CD4(+) T cell priming. In summary, we propose a model in which broad-based T cell-mediated responses upon vaccination can be maximized by codelivery of aggregated protein and TLR7/8 agonist, which together promote optimal antigen acquisition and presentation by multiple DC subsets in the context of critical proinflammatory cytokines

Host and Environmental Influences on Development of Disease

While many myxozoan parasites produce asymptomatic infections in fish hosts, several species cause diseases whose patterns of prevalence and pathogenicity are highly dependent on host and environmental factors. This chapter reviews how these factors influence pathogenicity and disease prevalence. Influential host factors include age, size and nutritional state. There is also strong evidence for host strains that vary in resistance to infection and that there is a genetic basis for resistance. A lack of co-evolutionary processes appears to generally underly the devastating impacts of diseases caused by myxozoans when introduced fish are exposed to novel parasites (e.g. PKD in rainbow trout in Europe) or when native fish are exposed to an introduced parasite (e.g. whirling disease in North America). Most available information on abiotic factors relates to water temperature, which has been shown to play a crucial role in several host parasite systems (e.g. whirling disease, PKD) and is therefore of concern in view of global warming, fish health and food sustainability. Eutrophication may also influence disease development. Abiotic factors may also drive fish disease via their impact on parasite development in invertebrate hosts

Diseases and Mortalities of Fishes and Other Animals In the Gulf of Mexico

Most mortality results from natural causes including red tide which is primarily restricted to West Florida and cold-kills that have greater influence in the warmer regions of South Texas and South Florida, but also kill a significant amount of fish and other animals in the northern Gulf. With the exception of red tide and other harmful algal blooms, the health of the Gulf has not been systematically studied. Mexico has only recently started to evaluate the health of its coastlines. Mortalities of marine animals, particularly fishes, in the Gulf caused by natural and anthropogenic events seem to interact with infectious disease agents and noninfectious diseases, but the mortalities are often attributed to the disease agents alone. “Events” that cause mortalities include eutrophication; hypoxia; algal blooms; temperature, salinity, and weather extremes; and chemical and sediment pollution. “Diseases” include those caused by infectious agents, parasites, neoplasms, and developmental abnormalities. Interactions of the effects of diseases and stressful events are considered important but little investigated