Folate, homocysteine, interleukin-6, and tumor necrosis factor alfa levels, but not the methylenetetrahydrofolate reductase C677T polymorphism, are risk factors for schizophrenia.

The methylenetetrahydrofolate reductase (MTHFR) C677T mutation has been associated to high homocysteine levels and schizophrenia. Since cytokines are altered in schizophrenia and increments of homocysteine could promote an inflammatory response, it was investigated whether interleukin-6 (IL-6) and tumor necrosis factor alfa (TNFalpha) levels are modulated by the MTHFR genotype. Serum levels of TNFalpha, IL-6, B(12), homocysteine, folate and red blood cell (RBC) folate as well as the MTHFR genotype were determined in a group of schizophrenic patients and compared to those of a control group. RBC folate levels were reduced and homocysteine and the two cytokines' concentrations were elevated in all patients as compared to controls. RBC folate in both heterozygous (CT) and homozygous (TT) patients was significantly different to that of their respective control groups. Homocysteine levels found in patients were significantly higher than those found in controls, only in individuals carrying the TT genotype. Cytokine levels were augmented in the group of patients irrespective of the genotype, and significant differences were found in all cases, except for TNFalpha levels in those subjects carrying the CC genotype. After adjusting for sex, low levels of RBC folate, high levels of homocysteine, both medium and high levels of TNFalpha and high IL-6 levels were associated with schizophrenia. MTHFR genotype was not a risk factor for developing the disease, although a larger sample is required to confirm this finding.

Aluminium phosphate potentiates the efficacy of DNA vaccines against Leishmania mexicana.

DNA vaccines have been able to induce partial protection against infection with Leishmania in mice, but it is still necessary to increase their efficacy. In the present study we evaluated aluminium phosphate as an adjuvant of different formulations and doses of DNA vaccines against L. mexicana in BALB/c mice. Aluminium phosphate had no effect on the humoral response induced by a high dose (100 microg) DNA vaccine, but slightly increased the cellular response and the protection against infection. It also allowed a non-immunoprotective low dose (20 microg) DNA vaccine encoding L. mexicana GP63 and Leishmania donovani NH36 to become protective. Aluminium phosphate may thus be an effective, low cost and safe adjuvant for DNA vaccines, and the vaccine formulation described here may be an excellent candidate for further vaccine development against Leishmania.

Cross-protective efficacy of a prophylactic Leishmania donovani DNA vaccine against visceral and cutaneous murine leishmaniasis.

The fucose-mannose ligand (FML) complex of Leishmania donovani is a promising vaccine candidate against murine and canine visceral leishmaniasis, and its main component is a 36-kDa nucleoside hydrolase (NH36). In this study, we tested the immune response and protection induced by the purified FML, the recombinant NH36 (rNH36), and NH36 DNA vaccines against the agents of visceral (L. chagasi) and cutaneous (L. mexicana) leishmaniasis in BALB/c mice. Mice developed weak humoral response to the vaccines alone, except for those immunized with FML. However, all three vaccine groups presented elevated immunoglobulin G (IgG), IgG1, and IgG2a levels after infection with L. chagasi, whereas no differences were observed between vaccine and control groups after infection with L. mexicana. A strong intradermal reaction to L. donovani and L. mexicana antigens was observed in mice immunized with rNH36 or FML, whereas mice immunized with NH36 DNA only reacted against L. donovani antigens. Experimental infection of immunized mice demonstrated that FML and rNH36 induced significant protection against L. chagasi infection with reductions in parasite loads of 79%. FML also conferred partial protection against L. mexicana infection. The best protection was observed in mice immunized with the VR1012-NH36 DNA vaccine, which induced an 88% reduction in L. chagasi parasite load and a 65% reduction in L. mexicana lesion size. Fluorescence-activated cell sorting analysis indicated the DNA vaccine induced a two- to fivefold increase in gamma interferon-producing CD4(+) T cells, indicating a Th1-type immune response. Our results showed that the NH36 DNA vaccine induced a strong immunoprotection against visceral and cutaneous leishmaniasis, suggesting that this DNA vaccine represents a very good candidate for use against several Leishmania species.