Vaccination against schistosomiasis and fascioliasis with the new recombinant antigen Sm14: potential basis of a multi-valent anti-helminth vaccine?

Molecular cloning of components of protective antigenic preparations have suggested that related parasite fatty acid binding proteins could form the basis of the well documented protective, immune cross reactivity between the parasitic trematode worms Fasciola hepatica and Schistosoma mansoni. We have now confirmed the cross protective potential of parasite fatty acid binding proteins and suggest that it may be possible to produce a single vaccine that would be effective against at least two parasites, F. hepatica and S. mansoni of veterinary and human importance respectively.

Anti-embryonation immunity in murine schistosomiasis japonica (Philippines)

The hypothesis that granuloma modulation and disease abatement in chronic infection with Schistosoma japonicum could be ascribed to antibody-mediated effects on egg maturation and egg viability, arose from studies performed with mice in the Philippines. This novel hypothesis has not yet been integrated into the schistosomiasis literature despite being formulated more than a decade ago. One reason for this is that the phenomenon might be confined to S. japonicum, even S. japonicum (Philippines).

Prevalence of anti-Taenia solium antibodies in sera from outpatients in an Andean region of Ecuador

Sera from 9,254 individuals that presented at one of three outpatient clinics in Quito, Ecuador were assayed by indirect hemagglutination for the presence of antibodies reactive with antigens from Taenia solium cysts. Immunoblot anlysis of 81 selected sera with IHA titers ranging from 0 to 1,028 showed that a titer of maior ou igual a 32 was suggestive of exposure to the parasite. Nine percent (9 %) of the 9,254 patients had titers of 32 or greater. Of 3,503 sera from one clinic, which included sera from food handlers undergoing yearly physicals, 390 (11 %) were positive. In addition, a correlation with age was seen in some, but not all, populations. In situations where age-related effects were noted, the highest incidence was seen in the youngest (0-20 years) and in the oldest (51-60 years) group. Thus, a resurgence of infection after a period of lower prevalence may be developing. Overall, this study shows that cysticercosis is relatively common and potentially a serious health problem in this region.

Antibodies anti Bloodstream and Circumsporozoite Antigens (Plasmodium vivax and Plasmodium malariae/P. brasilianum) in Areas of Very Low Malaria Endemicity in Brazil

During 1992-1994, 33 malaria cases were reported in two regions in Brazil where few sporadic atypical cases occur, most of them in home owners, who are weekenders, while home caretakers live there permanently. Indirect Fluorescent Antibody Test (IFAT), with Plasmodium vivax, and Enzime Linked Immunosorbent Assay (ELISA) with repeat peptides of the circumsporozoite (CS) proteins of the 3 known P. vivax variants and P. malarie/P. brasilianum, were performed on 277 sera, obtained within a 5 to 10 km range of malaria cases. Very rarely did any of these donors recall typical malaria episodes. Blood smears of all but 5 were negative. One of the 5 malaria cases included in our serology was of a home owner, 1 of a permanent resident, 3 from Superintendência de Controle de Endemias employees who went there to capture mosquitoes. In Region 1 the prevalence of IFAT positive sera was 73% and 28% among caretakers, 18% and 9.6% among home owners. In Region 2 (3 localities) no distinction was possible between caretakers and home owners, IFAT positivity being 38%, 28% and 7%. The relative percentage of positive anti-CS repeats ELISA, differed for each of the peptides among localities. Dwellings are in the vicinity of woods, where monkeys are frequently seen. The origin of these malaria cases, geographical differences and high seropositivity is discussed

Biomorphological Alterations Induced by an Anti-juvenile Hormonal Compound, 2-(2-EthoxyEthoxy)Ethyl Furfuryl Ether, on Three Species of Triatominae Larvae (Hemiptera, Reduviidae)

Applied topically to larvae of Rhodnius prolixus Stal, Triatoma infestans (Klug) and Panstrongylus herreri Wygodzinsky, vectors of Trypanosoma cruzi, the causative agent of Chagas'disease, a synthetic, furan-containing anti-juvenile hormonal compound, 2-(2-ethoxyethoxy)ethyl furfuryl ether induced a variety of biomorphological alterations, including precocious metamorphosis into small adultoids with adult abdominal cuticle, ocelli, as well as rudimentary adultoid wings. Some adultoids died during ecdysis and were confined within the old cuticle. The extension of these biomorphological responses is discussed in terms of the complexity of the action of anti-juvenile hormonal compounds during the development of triatomines

Pulmonary biology of anti-interleukin 5 antibodies

Interleukin 5 (IL-5) is a critical cytokine for the maturation of eosinophil precursors to eosinophils in the bone marrow and those eosinophils then accumulate in the lungs during asthma. We have studied anti IL-5 antibodies on allergic responses in mice, guinea pigs and monkeys and are extending this experiment into humans with a humanized antibody. In a monkey model of pulmonary inflammation and airway hyperreactivity, we found that the TRFK-5 antibody blocked both responses for three months following a single dose of 0.3 mg/kg, i.v. This antibody also blocked lung eosinophilia in mice by inhibiting release from the bone marrow. To facilitate multiple dosing and to reduce immunogenicity in humans, we prepared Sch 55700, a humanized antibody against IL-5. Sch 55700 was also active against lung eosinophilia in allergic monkeys and mice and against pulmonary eosinophilia and airway hyperresponsiveness in guinea pigs. Furthermore, as opposed to steroids, Sch 55700 did not cause immunosuppression in guinea pigs. Studies with this antibody in humans will be critical to establishing the therapeutic potential of IL-5 inhibition.

HIV Specific Humoral Immune Response in Rio de Janeiro, Brazil

Efforts to characterize HIV-1 polymorphism and anti-HIV immune response are being made in areas where anti-HIV/AIDS vaccines are to be employed. Anti-HIV-1 humoral immune response is being studied in infected individuals resident in Rio de Janeiro, in distinct cohorts involving recent seroconvertors, pregnant women or intravenous drug users (IDU). Comparative analyses of specificity of antibody response towards epitopes important for anti-HIV-1 immune response indicate quantitative differences between cohorts, with an exceptionally strong response in IDUs and weakest response in pregnant women. However, a comparative analysis between pregnant women cohorts from Rio de Janeiro and Rio Grande do Sul indicated an even lower response (with exception of the anti-V3-C clade peptide recognition) for the southern cohort. Studies analysing the immune function of the humoral response indicate a quite elevated occurrence of antibodies capable of neutralizing heterologous primary HIV-1 isolates from Rio de Janeiro. Attempts to correlate seroreactivity with HIV-1 neutralization with respect to HIV-1 polymorphism were not very successfull: while the Brazilian B clade B" variant could be recognized by binding assays, no significant distinction of HIV-1 clades/variants was observed in viral neutralization assays.

Quantitation of HIV-1 RNA Viral Load Using NASBA Methodology and Comparison with other Surrogate Markers for Disease Progression

In this study, HIV-1 viral load quantitation determined by Nucleic Acid Sequence Based Amplification (NASBA) was compared with other surrogate disease progression markers (antigen p24, CD4/CD8 cell counts and b-2 microglobulin) in 540 patients followed up at São Paulo, SP, Brazil. HIV-1 RNA detection was statistically associated with the presence of antigen p24, but the viral RNA was also detected in 68% of the antigen p24 negative samples, confirming that NASBA is much more sensitive than the determination of antigen p24. Regarding other surrogate markers, no statistically significant association with the detection of viral RNA was found. The reproducibility of this viral load assay was assessed by 14 runs of the same sample, using different reagents batches. Viral load values in this sample ranged from 5.83 to 6.27 log (CV = 36 %), less than the range (0.5 log) established to the determination of significant viral load changes.

Humoral Immune Response to the Anti-malaria Vaccine SPf66 in the Colombian Atrato River Region

The immunogenicity of anti-malaria synthetic vaccine SPf66 was tested in a region of the Colombian middle Atrato river. The specific serum antibodies against SPf66 were quantified in vaccinees and placebo injected controls for a two-years period post-immunization. The frequency of individuals showing seroconversion of anti-SPf66 antibodies three months after completion of the immunization schedule was higher in vaccinees than in controls (52.7% and 25.5%, respectively, p<0.01). However, an over than four-fold increase of the specific anti-SPf66 antibody titers was observed only in 1.4% of vaccinees and 0.2% of the controls (p<0.01). The anti-SPf66 antibody titers augmented in vaccinees from first dose application to three months after the third dose, continuously decreasing thereafter to reach below baseline values two years after completion of the immunization schedule. The results show that SPf66 has very low immunogenicity and induces a short term humoral immune response (six months).

Immunotherapy for Visceral Leishmaniasis: Ability of Factors Produced during Anti-leishmania Responses of Skin Test Positive Adults to Inhibit Peripheral Blood Mononuclear Cell Activities Associated with Visceral Leishmaniasis

The course of human Leishmania chagasi infections appears to be determined by the balance between type 1 (T1) CD4+ and CD8+ T suppressor (Ts) cell activities. Skin test positive adults living in hyperendemic areas who have no history of visceral leishmaniasis (VL) have T1 CD4+ T cell immunodominant responses against L. chagasi. The cytokines they secrete during anti-leishmania responses are a probable source of cytokines which inhibit the CD8+ Ts cells associated with VL. The ability of supernatants generated from peripheral blood mononuclear cells derived from skin test positive adults to reverse immune responses which appear to be mediated by CD8+ Ts cells was assessed in three sets of screening assays. The supernatants displayed three candidate factors. One, which could be explained by Leishmania antigens in the supernatant, decreased high endogenous IL-10 secretion characteristic of one class of VL patients. A second activity decreased high endogenous proliferation characteristic of the same class of patients without decreasing antigen specific proliferation. The third activity inhibited or killed CD8+ T cells but not CD4+ T cells. These activities might be useful in treating VL.

Adenosine Deaminase and Guanosine Deaminase Activities in Sera of Patients with Viral Hepatitis

In order to investigate purin and primidin metabolism pathways in hepatitis, adenosine deaminase (ADA) and guanosine deaminase (GDA) activities in sera of patients with different types and manifestations of viral hepatitis disease (A, B, C, D, E, chronic, acute) were investigated and compared with the control group of healthy individuals. Hepatitis cases were classified with respect to their serological findings and clinics. When compared all the hepatitis cases with the controls, levels of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase enzymes, as well as ADA and GDA, were significantly higher than the control group (p<0.01). Levels of ADA and GDA in hepatitis cases were determined as 26.07±11.98 IU/l and 2.37±1.91 IU/l, respectively. When compared their ADA and GDA levels amongst the classified hepatitis groups, there was no difference in ADA levels amongst cases (p>0.05). However, GDA levels in hepatitis A group were closed to the controls. Increase in serum ADA activities in hepatitis forms may be dependent on and reflect the increase in phagocytic activity of macrophages and maturation of T-lymphocytes, and may be valuable in monitoring in viral hepatitis cases.

Increased Pro-inflammatory Cytokines (TNF-a and IL-6) and Anti-inflammatory Compounds (sTNFRp55 and sTNFRp75) in Brazilian Patients during Exanthematic Dengue Fever

Pro-inflammatory cytokines, tumor necrosis factor (TNF-a), interleukin-6 (IL-6) and interleukin-1b (IL-1b) as well as anti-inflammatory compounds, soluble TNF-Receptor p55 (sTNFRp55), sTNFRp75 and IL-1 receptor antagonist (sIL-1Ra), were investigated in 34 Brazilian cases of dengue fever (DF) originated from a study of exanthematic virosis. The presence of pro-inflammatory cytokines was detected in sera from these patients by ELISA. TNF-a and IL-6 levels were significantly higher than control subjects in 32% and 52% patients, respectively. To our knowledge this was the first time a receptor antagonist and soluble receptors for cytokines were detected in sera obtained during exanthematic DF without hemorrhagic manifestations. Both sTNFRp55 and sTNFRp75 were consistently elevated in 42% and 84% patients, respectively. Most patients had IL-1b levels not different from those of normal subjects, except for one case. Only 16% patients had altered levels of IL-1Ra. Previous studies in dengue hemorrhagic fever patients demonstrated production of these soluble factors; here we observed that they are found in absence of hemorrhagic manifestations. The possible role of these anti-inflammatory compounds in immune cell activation and in regulating cytokine-mediated pathogenesis during dengue infection is discussed.