Acute Phase Response of Albumin and Haptoglobin in Experimental Infection of the Olive Baboon, Papio Anubis, with Schistosoma Mansoni

Following infection of baboons with Schistosoma mansoni cercariae, a rapid four-fold increase in mean  serum haptoglobin concentrations was observed. These concentrations dropped to near pre-infection levels  following curative treatment of the infected animals with praziquantel. On challenge of the animals with a  second cercarial dose, haptoglobin concentrations demonstrated a more gradual increase that did not attain  the heights of the initial infection. Albumin concentrations displayed an inversely disproportionate relationship  to those of haptoglobin and decreases were much less pronounced. Whereas albumin was not a  sensitive indicator of schistosomiasis mansoni, haptoglobin proved to be useful in detecting the acute infection  and in determining prognosis of the disease in the olive baboon.

Cellular and humoral immune responses and protection against schistosomes induced by a radiation-attenuated vaccine in chimpanzees

The radiation-attenuated Schistosoma mansoni vaccine is highly effective in rodents and primates but has never been tested in humans, primarily for safety reasons. To strengthen its status as a paradigm for a human recombinant antigen vaccine, we have undertaken a small-scale vaccination and challenge experiment in chimpanzees (Pan troglodytes). Immunological, clinical, and parasitological parameters were measured in three animals after multiple vaccinations, together with three controls, during the acute and chronic stages of challenge infection up to chemotherapeutic cure. Vaccination induced a strong in vitro proliferative response and early gamma interferon production, but type 2 cytokines were dominant by the time of challenge. The controls showed little response to challenge infection before the acute stage of the disease, initiated by egg deposition. In contrast, the responses of vaccinated animals were muted throughout the challenge period. Vaccination also induced parasite-specific immunoglobulin M (IgM) and IgG, which reached high levels at the time of challenge, while in control animals levels did not rise markedly before egg deposition. The protective effects of vaccination were manifested as an amelioration of acute disease and overall morbidity, revealed by differences in gamma-glutamyl transferase level, leukocytosis, eosinophilia, and hematocrit. Moreover, vaccinated chimpanzees had a 46% lower level of circulating cathodic antigen and a 38% reduction in fecal egg output, compared to controls, during the chronic phase of infection

Attenuated Leishmania induce pro-inflammatory mediators and influence leishmanicidal activity by p38 MAPK dependent phagosome maturation in Leishmania donovani co-infected macrophages

Promastigote form of Leishmania, an intracellular pathogen, delays phagosome maturation and resides inside macrophages. But till date limited study has been done to manipulate the phagosomal machinery of macrophages to restrict Leishmania growth. Attenuated Leishmania strain exposed RAW 264.7 cells showed a respiratory burst and enhanced production of pro-inflammatory mediators. The augmentation of pro-inflammatory activity is mostly attributed to p38 MAPK and p44/42 MAPK. In our study, these activated macrophages are found to induce phagosome maturation when infected with pathogenic Leishmania donovani. Increased co-localization of carboxyfluorescein succinimidyl ester labeled pathogenic L. donovani with Lysosome was found. Moreover, increased co-localization was observed between pathogenic L. donovani and late phagosomal markers viz. Rab7, Lysosomal Associated Membrane Protein 1, Cathepsin D, Rab9, and V-ATPase which indicate phagosome maturation. It was also observed that inhibition of V-type ATPase caused significant hindrance in attenuated Leishmania induced phagosome maturation. Finally, it was confirmed that p38 MAPK is the key player in acidification and maturation of phagosome in attenuated Leishmania strain preexposed macrophages. To our knowledge, this study for the first time reported an approach to induce phagosome maturation in L. donovani infected macrophages which could potentiate short-term prophylactic response in futur

Do schistosome vaccine trials in mice have an intrinsic flaw that generates spurious protection data?

The laboratory mouse has been widely used to test the efficacy of schistosome vaccines and a long list of candidates has emerged from this work, many of them abundant internal proteins. These antigens do not have an additive effect when co-administered, or delivered as SWAP homogenate, a quarter of which comprises multiple candidates; the observed protection has an apparent ceiling of 40–50 %. We contend that the low level of maturation of penetrating cercariae (~32 % for Schistosoma mansoni) is a major limitation of the model since 68/100 parasites fail to mature in naïve mice due to natural causes. The pulmonary capillary bed is the obstacle encountered by schistosomula en route to the portal system. The fragility of pulmonary capillaries and their susceptibility to a cytokine-induced vascular leak syndrome have been documented. During lung transit schistosomula burst into the alveolar spaces, and possess only a limited capacity to re-enter tissues. The acquired immunity elicited by the radiation attenuated (RA) cercarial vaccine relies on a pulmonary inflammatory response, involving cytokines such as IFNγ and TNFα, to deflect additional parasites into the alveoli. A principal difference between antigen vaccine protocols and the RA vaccine is the short interval between the last antigen boost and cercarial challenge of mice (often two weeks). Thus, after antigen vaccination, challenge parasites will reach the lungs when both activated T cells and cytokine levels are maximal in the circulation. We propose that “protection” in this situation is the result of physiological effects on the pulmonary blood vessels, increasing the proportion of parasites that enter the alveoli. This hypothesis will explain why internal antigens, which are unlikely to interact with the immune response in a living schistosomulum, plus a variety of heterologous proteins, can reduce the level of maturation in a non-antigen-specific way. These proteins are “successful” precisely because they have not been selected for immunological silence. The same arguments apply to vaccine experiments with S. japonicum in the mouse model; this schistosome species seems a more robust parasite, even harder to eliminate by acquired immune responses. We propose a number of ways in which our conclusions may be tested

Brine Shrimp Lethality Test of Soluble Proteis from Biomphalaria pfeifferi Snail as Preliminary for Vaccine Development for Schistosoma mansoni

The study tested for in vivo Brine Shrimp Lethality Test (BSLT) of soluble protein extracts from Biomphalaria pfeifferi snail. The proteins from foot and digestive gland were processed and their concentration determined by microtitre technique. Concentrations were 1.4 mg/ml for foot and 1.4 mg/ml for digestive gland extracts. Cytotoxicity of the proteins was evaluated in terms of Lethality concentration (LC50) using10µg/ml,100µg/ml and 1000µg/ml concentrations of the proteins. Ten Brine Shrimps larvae (nauplii) were placed in duplicate tubes of each concentration. After 24 hours the surviving Brine Shrimps larvae were counted and LC50 was determined by Finney computer program at 95% confidence interval. The results showed foot and digestive gland proteins had a LC50 of 71.43µg/ml and 52.18µg/ml respectively. The results imply bioactive components are present in the proteins with probable larvicidal activity. As per the results, the proteins can be used as schistosomiasis vaccine candidates

Immunopathological effects of some Biomphalaria pfeifferi proteins against Schistosoma mansoni infection in BALB/c mice

Intestinal schistosomiasis remains a major cause of morbidity and mortality in most parts of the world, despite decades of widespread chemotherapy use. The present study determined the intermediate host proteins expressing the immunogenic properties against the parasite by determining the efficacy. Digestive gland and foot parts were isolated by dissection from the Biomphalaria pfeifferi, processed and the concentration was determined. The proteins were used to immunize the experimental groups of BALB/c mice which were then challenged with the parasite to determine the efficacy. The results show the proteins were efficacious with foot and digestive gland soluble proteins having 59.1 and 40.9% worm reduction, respectively. They also stimulated the production of effective cytokines, immunoglobulins and reduced hepatic pathology

Cellular responses against Schistosoma mansoni in immunized Balb/c mice with soluble proteins from intermediate host, Biomphalaria pfeifferi

Scores of millions of people around the world are infected by Schistosoma mansoni causing considerable morbidity, mortality and loss of productivity. Safe chemotherapeutic agents have been used though there are challenges of re-infection due to resistance. Both epidemiological and experimental data suggest that acquired cell mediated immunity play significant roles in regulating the intensity of S. mansoni infection as well as its patho-physiologic sequelae. Improved control of this trematode parasite may be obtained with immunization to enhance the resistance of individuals to risk of infection. This study investigated the cellular responses of mice immunized with soluble proteins from foot and digestive gland of the vector snail and challenged with S. mansoni. The proteins were used to immunize the experimental groups then challenged with the S. mansoni. The experimental groups were FT (immunized with foot protein) and DG (immunized with digestive gland). The parameters, which were analyzed to demonstrate protection, included; the worm counts and cellular (IFN-γ, IL-5 cytokines) responses. It was observed that, the experimental groups showed significant protection in terms of worm reduction and immune responses. The group vaccinated with foot protein showed higher protection (87.5%) as compared to the group vaccinated with the digestive gland (50%) in terms of worm reduction. Cytokines (IFN-γ and IL-5) production was present in different levels during the assay time points which showed an aspect of protection. The Foot protein of the vector showed more immunizing power than the digestive gland. Research towards utilizing the two proteins as feasible vaccine candidates is encouraged

Gross and Histopathological Findings in Cercopithecus Aethiops with Experimental Cyclospora Infection in Kenya

Journal ArticleIn 2009, experimental Cyclospora infections were established in two juvenile female and two adult male Cercopithecus aethiops (African green monkeys) at Nairobi’s Institute of Primate Research (IPR). The study animals were humanely sacrificed, and gross and histopathological evaluation was done at seven weeks post-infection. On gross examination, the juveniles had no abnormalities except for a slight enlargement of the mesenteric lymph nodes, while the adults displayed more pathology of enlarged lymph nodes, hemorrhagic gastrointestinal tracts, widespread necrotic foci of the liver, and enlarged spleens. Significant histopathological findings were observed in both the juveniles and adults, which ranged from mild inflammatory reactions in the stomach and intestines to intense cellular infiltrations with mitotic activity and lymphocytic infiltrations around the periportal area of the livers. The lymph nodes had extensive hyperplasia with many mitotic cells