Correlates of GLA family adjuvants' activities.

Lipopolysaccharide (LPS) is a well-defined agonist of Toll-like receptor (TLR) 4 that activates innate immune responses and influences the development of the adaptive response during infection with Gram-negative bacteria. Many years ago, Dr. Edgar Ribi separated the adjuvant activity of LPS from its toxic effects, an effort that led to the development of monophosphoryl lipid A (MPL). MPL, derived from Salmonella minnesota R595, has progressed through clinical development and is now used in various product-enabling formulations to support the generation of antigen-specific responses in several commercial and preclinical vaccines. We have generated several synthetic lipid A molecules, foremost glucopyranosyl lipid adjuvant (GLA) and second-generation lipid adjuvant (SLA), and have advanced these to clinical trial for various indications. In this review we summarize the potential and current positioning of TLR4-based adjuvant formulations in approved and emerging vaccines.

Hepatitis B virus infection among immunocompromised patients in Egypt.

Several workers reported an increased susceptibility to hepatitis B virus (HBV) in immunosuppressed patients. A study was carried out on 4 groups of supposedly immunocompromised patients for hepatitis B surface antigen (HBsAg), and anti-HBs. The 4 groups of patients were suffering from: Leprosy, Bronchial asthma, Diabetes and hepatosplenic Schistosomiasis. Serum specimens were obtained from 137 patients representing the 4 groups and from a control group of 25 healthy individuals. All sera were tested by ELISA technique for HBsAg and anti-HBs. Results indicated that HBsAg carrier rate was 4% for the control healthy group, 7% for Bronchial asthma, 10% for Diabetes, 24% for Leprosy and 28% for hepatosplenic Schistosomiasis. On the other hand, the anti-HBs was 21% for the control group, 29% for Schistosomiasis, 55% and 58% for Diabetes and Bronchial asthma respectively and 74% for Leprosy. This study shows that immunosuppressed patients particularly those suffering from leprosy and hepatosplenic Schistosomiasis experience higher HBsAg carrier rate than the control group for the endemic hepatitis B (6-7 times higher for leprosy and Schistosomiasis). An important observation was the diminished anti-HBs rate in hepatosplenic Schistosomiasis patients, despite the highest HBsAg carrier rate they exhibited. This may be due to an immunological defect, resulting in an unsatisfactory antibody response and chronic hepatitis B antigenemia. In Egypt, where Schistosomiasis is prevalent (40-50%), the problems caused by hepatitis B infection are increased.

Leishmania major: solid phase radioimmunoassay for antibody detection in human cutaneous leishmaniasis.

A radioimmunoassay for the quantitative determination of antileishmanial antibody in sera from patients suffering from cutaneous leishmaniasis was developed. The assay, using as antigen either the soluble fraction from freeze-thawed sonicated Leishmania major (LRC-L137) promastigotes or a carbohydrate-lipid containing fraction obtained by extraction with hexane-isopropanol, was shown to be sensitive and reproducible. The sera of 95 patients were examined. These were from patients with cutaneous leishmaniasis (26 from the Jordan Valley and 13 from Sinai), kala-azar (9), malaria (24), schistosomiasis (10), toxoplasmosis (5), and leprosy (8); controls were 37 normal human sera. No significant antigen dependent differences were observed using sera from cutaneous leishmaniasis patients, although differences in the immunological response were observed between the two populations of these patients. Antileishmanial activity was not detected in sera from patients with malaria, schistosomiasis, or toxoplasmosis. Although sera from leprosy patients crossreacted with the carbohydrate-lipid containing fraction, it was nevertheless more strain specific than freeze thawed sonicated L. major.

Immunopathology of parasitic diseases: a conceptual approach.

These studies would indicate tremendous variations in the clinical manifestations of parasitic disease, resulting from characteristics of the parasite, the host, and their interaction. They further suggest that the conceptual mechanistic model described in the introduction is highly applicable. Previous evidence to substantiate the validity of such a model in schistosomiasis, a variety of protozoan diseases, and leprosy has already been presented (Phillips and Fox, 1982). This report would appear to lend additional credence to the postulates and suggests that upon scrutiny, the model represents a reasonable explanation for a wide variety of clinical manifestations of a parasitic disease. In addition, it may provide a working hypothesis for the interpretation of the immunopathology found in other diseases such as filariasis. Figure 3 compares and contrasts schistosomiasis and filariasis within the context of this hypothesis. Immunopathology results from the relative balance of host-parasite immunogenic factors and modulatory specific and nonspecific factors. The resultant immunopathology results from a number of immunologic mechanisms, but for the sake of comparison can be placed in certain analogous groups. Clearly, although a number of experimental questions still exist, vis-à-vis these analogies, it would appear that they are reasonable comparisons. It is hoped that such a conceptual approach might provide a useful framework for an understanding of the spectrum of immunopathology resulting from parasitic disease. These concepts might possibly lead to the eventual control of immunopathology.

[Distribution of HBs antigen in Tananarive (author's transl)]. / Répartition de l'antigène HBs à Tananarive.

This survey has been conducted among blood donors and patients with hepatitis, cirrhosis, liver carcinomas and various causes of liver dysfunction or enlargement. The frequency is 5,4 p. 100 among blood donors and 50 p. 100 among cases of hepatitis.

[Relations between hepatitis B surface antigen and parasitic diseases: observations in patients with ancylostomiasis and schistosomiasis]. / Rapporti tra HBsAg e parassitosi: osservazioni in pazienti con anchilostomiasi e con schistosomiasis.

Hepatitis B antigen carriage was studied in Somalia in 155 patients with ancylostomiasis, with urinary schistosomiasis and with leprosy (lepromatosus and tuberculoid type and leprosy with schistosomiasis). The results have showed a significantly (p less than 0,001) higher frequency of HBsAg among the patients with ancylostomiasis (33,33%) and with urinary schistosomiasis (25,92%) than either the leprosy patients (9,67% in the L type and 6,89% in the T type) or the controls (11,11%); in the leprosy patients with schistosomiasis the frequency was 40,0%. The role of some penetrating skin parasites in the epidemiology of hepatitis B was discussed.