Summary Visceral leishmaniasis (VL) is a disease transmitted by phlebotomine sand flies, fatal if untreated, and with no available human vaccine. In rodents, cellular immunity to Leishmania parasite proteins as well as salivary proteins of the sand fly is associated with protection, making them worthy targets for further exploration as vaccines. This review discusses the notion that a combination vaccine including Leishmania and vector salivary antigens may improve vaccine efficacy by targeting the parasite at its most vulnerable stage just after transmission. Furthermore, we put forward the notion that better modeling of natural transmission is needed to test efficacy of vaccines. For example, the fact that individuals living in endemic areas are exposed to sand fly bites and will mount an immune response to salivary proteins should be considered in pre-clinical and clinical evaluation of leishmaniasis vaccines. Nevertheless, despite remaining obstacles there is good reason to be optimistic that safe and effective vaccines against leishmaniasis can be developed.
Cellular immune responses were studied in 35 Brazilian patients with either active cutaneous leishmaniasis (CL), active mucosal leishmaniasis (ML), or healed cutaneous leishmaniasis. The mean age and duration of illness in the two groups were as follows: 14 CL patients, age 28 +/- 13 yr, disease 5 +/- mo; and 16 ML patients, age 34 +/- 15 yr, disease 86 +/- 117 mo. Patients with CL and ML responded well to leishmania antigen in blastogenesis assays. However, the response of ML patients was over three times greater than the response of CL patients. There was a significant correlation between the magnitude of the lymphoproliferative response and the duration of disease activity. There were no significant differences between CL and ML patients in terms of the following parameters: lymphoproliferative responsiveness to mitogens (phytohemagglutinin, concanavalin A, and pokeweed mitogen) and peripheral blood lymphocyte subpopulations (T and B cells, oKT8+ and OKT4+ cells, OKT4:OKT8 ratio). Peripheral blood mononuclear cells from ML patients also generated interferon-gamma containing lymphokine in response to stimulation with leishmania antigen. This lymphokine was capable of inducing macrophages from ML patients to inhibit the intracellular multiplication of leishmania in vitro. These studies have determined that the parameters of lymphocyte and macrophage functions evaluated in ML and CL patients are comparable, except for an enhanced lymphoproliferative response, with leishmania antigen in ML patients. This later finding may be a function of the long duration of active disease in this population and unrelated to the pathogenesis of their mucosal lesions.
Newer genetic lines of pigs are being used in indoor and outdoor production systems. The objectives of Exp. 1 were to describe the effects of the maternal sow line genotype, environment (indoor vs outdoor), and the genotype x environment interactions on blood hemoglobin (Hb), immunoglobulin G (IgG) concentrations, white blood cell (WBC) numbers, lymphocyte transformation/blastogenesis (LTA), natural killer (NK) cell activity, neutrophil chemotaxis, cortisol concentrations, and leukocyte differentials. Studies were performed using two genotypes: PIC Experimental-94 (Exp-94, an experimental line containing 25% Meishan) and PIC Camborough-15 (C-15). The Exp-94 sows had lower LTA at 0.2 microg/mL mitogen than the C-15 sows, whereas Exp-94 sows had higher NK cytotoxicity than the C-15 sows. When indoors, the two genotypes showed similar neutrophil chemotaxis. When outdoors, the C-15 genotype had higher (P < .01) neutrophil chemotaxis than the Exp-94 sows. The other immune measures were statistically similar for the two genotypes for each environment and for the genotype x environment interaction of sows. Experiment 2 sought to determine the effects of genotype on the immune system of nursery-age offspring of the experimental lines. Each sow line was bred to a common PIC 405 boar line. The Exp-94 x 405 pigs had elevated WBC numbers than C-15 x 405 pigs. The social status of the Exp-94 x 405 or the C-15 x 405 pigs showed no effect on any of the immune measures studied. The other immune measures were statistically similar for the two lines of pigs. The Exp-94 line had marginally increased NK activity but reduced lymphocyte blastogenesis and neutrophil chemotaxis compared with the C-15 line.
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