8 research outputs found
Development of a vaccine strategy against human and bovine schistosomiasis: background and update
Systemic and Mucosal Responses to Oral Administration of Excretory and Secretory Antigens from Giardia intestinalis
Giardia, a flagellated protozoan that infects the upper small intestine of its vertebrate host, is the most common parasitic protist responsible for diarrhea worldwide. Molecules released by the parasite, particularly excretory and secretory antigens, seemed to be associated with pathogenesis as well as with the expression of Giardia virulence. In the present work, we examined the effect of oral administration of Giardia intestinalis excretory and secretory antigens on systemic and local antibody response as well as on mucosal injuries in BALB/c mice. Significant titers of serum-specific immunoglobulin G1 (IgG1) and specific IgG2a were observed. Systemic and mucosal specific IgA antibodies were also recorded. A transient production of serum-specific IgE antibody and high total IgE levels were also detected, suggesting the presence in excretory and secretory proteins of factors promoting a specific IgE response. The sera of excretory and secretory antigen-treated mice recognized proteins of 50 and 58 kDa as well as electrophoretic bands of 15, 63, and 72 kDa that could support a proteinase activity. The in vitro exposure of G. intestinalis trophozoites to heat-inactivated sera from mice orally inoculated with excretory and secretory antigens induced a decrease of growth, revealing a complement-independent inhibitory activity of specific serum antibodies. Furthermore, histological evaluation performed on the small and large intestines revealed moderate to acute histological changes comparable to those observed in natural or experimental Giardia infection characterized by eosinophilic infiltration, hypercellularity, and enterocytic desquamation. The present results suggested that Giardia excretory and secretory antigens stimulate a preferential Th2 response, which is probably involved in the intestinal alterations associated with giardiasis
Development of a Vaccine Strategy against Human and Bovine Schistosomiasis. Background and Update
Schistosomiasis is a chronic and debilitating parasitic disease that
affects over 200 million people throughout the world and causes about
500 000 deaths annually. Two specific characteristics of schistosome
infection are of primordial importance to the development of a vaccine:
schistosomes do not multiply within the tissues of their definitive
hosts (unlike protozoan parasites) and a partial non- sterilizing
immunity can have a marked effect on the incidence of pathology and on
disease transmission. Since viable eggs are the cause of disease
pathology, a reduction in worm fecundity whether or not accompanied by
a reduction in parasite burden is a sufficient goal for vaccine induced
immunity. We originally showed that IgE antibodies played in
experimental models a pivotal role for the development of protective
immunity. These laboratory findings have been now confirmed in human
populations. Following the molecular cloning and expression of a
protein 28 kDa protein of Schistosoma mansoni and its identification as
a glutathion S- transferase, immunization experiments have been
undertaken in several animal species (rats, mice, baboons). Together
with a significant reduction in parasite burden, vaccination with Sm28
GST was recently shown to reduce significantly parasite fecundity and
egg viability leading to a decrease in liver pathology. Whereas IgE
antibodies were shown to be correlated with protection against
infection, IgA antibodies have been identified as one of the factors
affecting egg laying and viability. In human populations, a close
association was found between IgA antibody production to Sm28 GST and
the decrease of egg output. The use of appropriate monoclonal antibody
probes has allowed the demonstration that the inhibition of parasite
fecundity following immunization was related to the inhibition of
enzymatic activity of the molecule. Epitope mapping of Sm28 GST has
indicated the prominent role of the N and C terminal domains.
Immunization with the corresponding synthetic peptides was followed by
a decrease of 70 % of parasite fecundity and egg viability. As a
preliminary step towards phase I human trials, vaccination experiments
have been performed in cattle, a natural model for Schistosoma bovis.
Vaccination of calves with the S. bovis GST has led to a reduction of
over 80 % of egg output and tissue egg count. Significant levels of
protection were also observed in goats after immunization with the
recombinant S. bovis GST. Increasing evidence of the participation of
IgA antibodies in protective immunity has prompted us toward the
development of mucosal immunization. Preliminary results indicate that
significant levels of protection can be achieved following oral
immunization with live attenuated vectors or liposomes. These studies
seem to represent a promising approach towards the future development
of a vaccine strategy against one of the major human parasitic
diseases
Antioxidants other than vitamin c may be detected by glucose meters: immediate relevance for patients with disorders targeted by antioxidant therapies
International audienceOwing to their ease of use, glucose meters are frequently used in research and medicine. However, little is known of whether other non-glucose molecules, besides vitamin C, interfere with glucometry. Therefore, we sought to determine whether other antioxidants might behave like vitamin C in causing falsely elevated blood glucose levels, potentially exposing patients to glycemic mismanagement by being administered harmful doses of glucose-lowering drugs. To determine whether various antioxidants can be detected by seven commercial glucose meters, human blood samples were spiked with various antioxidants ex vivo and their effect on the glucose results were assessed by Parkes error grid analysis. Several of the glucose meters demonstrated a positive bias in the glucose measurement of blood samples spiked with vitamin C, N-acetylcysteine, and glutathione. With the most interference-sensitive glucose meter, non-blood solutions of 1 mmol/L N-acetylcysteine, glutathione, cysteine, vitamin C, dihydrolipoate, and dithiothreitol mimicked the results seen on that glucose meter for 0.7, 1.0, 1.2, 2.6, 3.7 and 5.5 mmol/L glucose solutions, respectively. Glucose meter users should be alerted that some of these devices might produce spurious glucose results not only in patients on vitamin C therapy but also in those being administered other antioxidants. As discussed herein, the clinical relevance of the data is immediate in view of the current use of antioxidant therapies for disorders such as the metabolic syndrome, diabetes, cardiovascular diseases, and coronavirus disease 2019