Treatment with bovine hyperimmune colostrum of cryptosporidial diarrhea in AIDS patients

Nord, Jill A.; Ma, Pearl; DiJohn, David; Tzipori, Saul; Tacket, Carol O.

doi:10.1097/00002030-199006000-00015

Cited by 126 publications

(74 citation statements)

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“…Additional studies will be required to explain these unexpected observations. In any case, a compelling rationale for the use of MAb formulations targeting up to three distinct antigens rather than single MAbs is evident when considering the extended-course treatment regimens which are likely to be required for control of infection in immunodeficient hosts (8,27,35,36,51,52,53,57). If antigenic variation within or between C. parvum isolates occurs, targeting multiple epitopes with therapeutic MAbs may reduce the potential for selection and emergence of variant C. parvum subpopulations.…”

Section: Discussionmentioning

confidence: 99%

“…In previous studies, bovine colostral antibody preparations produced against whole C. parvum organisms have demonstrated specific neutralizing activity in vitro and highly significant efficacy against infection in animal models when evaluated under controlled conditions (11,12,33,34,36,51). The efficacy of such preparations in persistently infected immunodeficient humans has been demonstrated but has been inconsistent in a limited number of studies, due in part to confounding patient and treatment variables (8,27,29,35,52,53). While these early observations provided the rationale to investigate passive antibody-based immunization for cryptosporidiosis, possible limitations to the use of polyclonal antibodies produced against uncharacterized whole C. parvum preparations include the relatively low content of specific neutralizing antibodies in the immunoglobulin fraction, logistical restraints on production in quantity, and lot-to-lot heterogeneity in therapeutic predictability (6,35,59).…”

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confidence: 99%

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Characterization and Formulation of Multiple Epitope-Specific Neutralizing Monoclonal Antibodies for Passive Immunization against Cryptosporidiosis

2000

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The coccidian parasite Cryptosporidium parvum causes diarrhea in humans, calves, and other mammals. Neither immunization nor parasite-specific pharmaceuticals that are consistently effective against this organism are available. While polyclonal antibodies against whole C. parvum reduce infection, their efficacy and predictability are suboptimal. We hypothesized that passive immunization against cryptosporidiosis could be improved by using neutralizing monoclonal antibodies (MAbs) targeting functionally defined antigens on the infective stages. We previously reported that the apical complex and surface-exposed zoite antigens CSL, GP25-200, and P23 are critical in the infection process and are therefore rational targets. In the present study, a panel of 126 MAbs generated against affinity-purified CSL, GP25-200, and P23 was characterized to identify the most efficacious neutralizing MAb formulation targeting each antigen. To identify neutralizing MAbs, sporozoite infectivity following exposure to individual MAbs was assessed by enzyme-linked immunosorbent assay. Of 126 MAbs evaluated, 47 had neutralizing activity. These were then evaluated individually in oocystchallenged neonatal mice, and 14 MAbs having highly significant efficacy were identified for further testing in formulations. Epitope specificity assays were performed to determine if candidate MAbs recognized the same or different epitopes.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Characterization and Formulation of Multiple Epitope-Specific Neutralizing Monoclonal Antibodies for Passive Immunization against Cryptosporidiosis

2000

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“…A few case reports have suggested that hyperimmune bovine colostrum may modify the disease course of Cryptosporidium infection in immunocompromised hosts (Greenberg, 1996;Nord, 1990). Results obtained from bovine colostrum antibody therapy are mostly contradictory.…”

Section: Antibody Therapymentioning

confidence: 99%

Drug treatment and novel drug target againstCryptosporidium

Gargala

2008

Parasite

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Summary :Cryptosporidiosis emergence triggered the screening of many compounds for potential anti-cryptosporidial activity in which the majority were ineffective. The outbreak of cryptosporidiosis which occurred in Milwaukee in 1993 was not only the first significant emergence of Cryptosporidium spp. as a major human pathogen but also a huge waterborne outbreak thickening thousands of people from a major city in North America. Since then, outbreaks of cryptosporidiosis are regularly occurring throughout the world. New drugs against this parasite became consequently urgently needed. Among the most commonly used treatments against cryptosporidiosis are paromomycin, and azithromycin, which are partially effective. Nitazoxanide (NTZ)'s effectiveness was demonstrated in vitro, and in vivo using several animal models and finally in clinical trials. It significantly shortened the duration of diarrhea and decreased mortality in adults and in malnourished children. NTZ is not effective without an appropriate immune response. In AIDS patients, combination therapy restoring immunity along with antimicrobial treatment of Cryptosporidium infection is necessary. Recent investigations focused on the potential of molecular-based immunotherapy against this parasite. Others tested the effects of probiotic bacteria, but were unable to demonstrate eradication of C. parvum. New synthetic isoflavone derivatives demonstrated excellent activity against C. parvum in vitro and in a gerbil model of infection. Newly synthesized nitroor non nitro-thiazolide compounds, derived from NTZ, have been recently shown to be at least as effective as NTZ against C. parvum in vitro development and are promising new therapeutic agents.

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“…15). Antibody preparations against candidiasis 16 and cryptosporidiosis [25][26][27][28][29] have also been successfully employed in immunocompromised patients.…”

Section: Discussionmentioning

confidence: 99%

Fungal prophylaxis by reduction of fungal colonization by oral administration of bovine anti-Candida antibodies in bone marrow transplant recipients

Tollemar

Gross

Dolgiras

et al. 1999

Bone Marrow Transplant

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Summary:Candida overgrowth and invasion constitute a serious threat with a high mortality in BMT recipients. Currently available topical antifungal prophylaxis is largely ineffective, and as resistance to existing, absorbable drugs for systemic use is rapidly developing, new forms of therapy are needed. We investigated the effect of oral treatment of BMT recipients with a bovine immunoglobulin product derived from animals immunized against several Candida species. The natural Candida colonization was first followed in 19 patients to establish the colonization pattern. Half of the patients were found to be colonized prior to transplantation and altogether 72% were colonized at some point during follow-up. Those with a high pre-transplant concentration of Candida in saliva (Ͼ100 CFU/ml) remained colonized throughout the BMT treatment period. The therapeutic effect was monitored in two other patient groups. The first group consisted of nine patients, where, due to a low number of primary colonized patients, response in colonized patients was suggestive of a therapeutic effect. In the second group, 10 patients with a high level of colonization (Ͼ100 CFU/ml) were given 10 g daily of the product in three divided doses. The results suggest a treatment-related reduction in Candida colonization in a majority (7/10) of patients and one patient became completely negative. As no adverse effects were noted, our findings encourage additional studies in immunocompromised, transplant patients.

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Treatment with bovine hyperimmune colostrum of cryptosporidial diarrhea in AIDS patients

Cited by 126 publications

References 0 publications

Characterization and Formulation of Multiple Epitope-Specific Neutralizing Monoclonal Antibodies for Passive Immunization against Cryptosporidiosis

Characterization and Formulation of Multiple Epitope-Specific Neutralizing Monoclonal Antibodies for Passive Immunization against Cryptosporidiosis

Drug treatment and novel drug target againstCryptosporidium

Fungal prophylaxis by reduction of fungal colonization by oral administration of bovine anti-Candida antibodies in bone marrow transplant recipients

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