Hyperimmune bovine colostrum specific for recombinant Cryptosporidium parvum antigen confers partial protection against cryptosporidiosis in immunosuppressed adult mice

Jenkins, Mark C.; O’Brien, Celia; Trout, James M.; Guidry, A.J.; Fayer, Ronald

doi:10.1016/s0264-410x(98)00369-7

Cited by 60 publications

(34 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additional studies will be required to further define the relationship between the antigens comprising GP25-200 and CSL. Recognition of carbohydrate-dependent epitopes by many ␣GP25-200 MAbs was not unexpected, based on the glycosylated state reported for C. parvum sporozoite apical and surface proteins (20,35,48,49) and observations that glycoconjugates are important targets of the humoral immune response against C. parvum (17,19,34,35,37,38,39,49,57). Recognition of peptide epitopes by all 14 Western blot-reactive ␣P23 MAbs is consistent with the reported presence of a single N-glycosylation site in P23 (31).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

2000

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

“…The role of C. parvum in diarrhearelated morbidity in AIDS patients and its economic impact on livestock production are now well recognized (13). No approved parasite-specific drugs, vaccines, or immunotherapies for C. parvum are presently available, although recent advances have been reported (4,8,15,17,30,32,35,41,50,57).…”

mentioning

confidence: 99%

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

2000

View full text Add to dashboard Cite

show abstract

“…Several such proteins have been identified as potential targets for active and/or passive immunoprophylaxsis and immunotherapy for cryptosporidiosis (5,8,10,26,39,69,(84)(85)(86)107). In particular, two antigen families, a 15-kDa group and a 27-kDa group, have consistently been identified by convalescent sera from infected humans and animals (48, 50, 54-56, 65, 67, 80, 82), and these specific humoral responses have been hypothesized to be associated with protection from subsequent infection and/or amelioration of disease (56).…”

Section: Discussionmentioning

confidence: 99%

“…HBC Ig inhibits sporozoite invasion in vitro and neutralizes sporozoite infectivity in animal models of cryptosporidiosis (5, 9, 10, 23, 69-71, 84-86, 107). Although the exact identities of the HBC Ig neutralization antigens are unknown, several candidate molecules have been identified (8,39,69,(84)(85)(86)107). The majority are protein or glycoprotein antigens present on the zoite surface or resident in the secretory organelles of the zoite apical complex, and several are secreted during gliding motility and/or epithelial cell invasion.…”

mentioning

confidence: 99%

Cloning and Sequence Analysis of a Highly PolymorphicCryptosporidium parvumGene Encoding a 60-Kilodalton Glycoprotein and Characterization of Its 15- and 45-Kilodalton Zoite Surface Antigen Products

2000

View full text Add to dashboard Cite

The apicomplexan parasite Cryptosporidium parvum is a major cause of serious diarrheal disease in both humans and animals. No efficacious chemo-or immunotherapies have been identified for cryptosporidiosis, but certain antibodies directed against zoite surface antigens and/or proteins shed by gliding zoites have been shown to neutralize infectivity in vitro and/or to passively protect against, or ameliorate, disease in vivo. We previously used monoclonal antibody 11A5 to identify a 15-kDa surface glycoprotein that was shed behind motile sporozoites and was recognized by several lectins that neutralized parasite infectivity for cultured epithelial cells. Here we report the cloning and sequence analysis of the gene encoding this 11A5 antigen. Surprisingly, the gene encoded a 330-amino-acid, mucin-like glycoprotein that was predicted to contain an N-terminal signal peptide, a homopolymeric tract of serine residues, 36 sites of O-linked glycosylation, and a hydrophobic C-terminal peptide specifying attachment of a glycosylphosphatidylinositol anchor. The singlecopy gene lacked introns and was expressed during merogony to produce a 60-kDa precursor which was proteolytically cleaved to 15-and 45-kDa glycoprotein products that both localized to the surface of sporozoites and merozoites. The gp15/45/60 gene displayed a very high degree of sequence diversity among C. parvum isolates, and the numerous single-nucleotide and single-amino-acid polymorphisms defined five to six allelic classes, each characterized by additional intra-allelic sequence variation. The gp15/45/60 single-nucleotide polymorphisms will prove useful for haplotyping and fingerprinting isolates and for establishing meaningful relationships between C. parvum genotype and phenotype.Cryptosporidium parvum, a protozoan parasite of the phylum Apicomplexa, is an enteric pathogen that infects humans and many animals and causes an acute diarrheal disease (30, 61). Cryptosporidiosis is self-limiting in immunocompetent individuals (22,25,116) but is often chronic and life-threatening in immunocompromised patients, such as those with AIDS (20,22,72,76,78) or in persons with weakened immune systems, for example, malnourished children and the elderly (18,24,27,46,89). Despite exhaustive attempts at chemotherapy with a wide variety of drugs, including many that are effective against related apicomplexan parasites, no efficacious treatment for cryptosporidiosis has been identified. Passive immunotherapy with hyperimmune bovine colostral immunoglobulin (HBC Ig) has, however, shown some ability to ameliorate the clinical symptoms of disease in humans (29,62,77,88,93,(108)(109)(110). HBC Ig inhibits sporozoite invasion in vitro and neutralizes sporozoite infectivity in animal models of cryptosporidiosis (5, 9, 10, 23, 69-71, 84-86, 107). Although the exact identities of the HBC Ig neutralization antigens are unknown, several candidate molecules have been identified (8,39,69,(84)(85)(86)107). The majority are protein or glycoprotein antigens present on the zoite surface ...

show abstract

“…In the present study, we hypothesized that passive immunotherapy against persistent C. parvum infection could be enhanced by targeting antigens known to function in the infection process. Because surface-exposed and apical complex antigens are critical to infection, they are opportune targets for immunization against C. parvum (7,10,18,34,36,37,39,42,46,47,53,57,61,62,64,66,67,74,80) as well as other apicomplexan parasites (5,14,15,23,25,46,68). Therefore, neutralizing MAbs against the surface pellicle antigen P23, the apical glycoprotein antigen complex GP25-200, and the apical complex glycoprotein CSL were prepared for therapeutic evaluation.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Monoclonal Antibodies against Defined Antigens for Passive Immunotherapy of Chronic Gastrointestinal Cryptosporidiosis

Riggs

Schaefer

Kapil

et al. 2002

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Cryptosporidium parvum is an important cause of diarrhea in humans and calves and can persistently infect immunocompromised hosts. Presently, there are no consistently effective parasite-specific drugs for cryptosporidiosis. We hypothesized that neutralizing monoclonal antibodies (MAbs) targeting the apical complex and surface antigens CSL, GP25-200, and P23 could passively immunize against cryptosporidiosis. We recently reported that a formulation of MAbs 3E2 (anti-CSL), 3H2 (anti-GP25-200), and 1E10 (anti-P23) provided significant additive prophylactic efficacy over that of the individual MAbs in neonatal ICR mice. In the present study, these MAbs were evaluated for therapeutic efficacy against persistent infection in adult gamma interferon-depleted SCID mice. 3E2 demonstrated the most significant and consistent therapeutic effect, reducing intestinal infection in two experiments. In one experiment, 3E2 plus 3H2 and 3E2 plus 3H2 plus 1E10 also significantly reduced infection; however, no significant increase in efficacy over 3E2 alone was apparent. The results indicate that anti-CSL MAb 3E2 has highly significant efficacy in reducing, but not eliminating, persistent C. parvum infection.The apicomplexan parasite Cryptosporidium parvum infects the intestinal tract in humans and calves and other agriculturally important animals and is a leading cause of diarrhea throughout the world (30). In neonates, the elderly, and hosts having congenital or acquired immunodeficiencies, the disease may become chronic and life-threatening (30, 59). Dissemination to extraintestinal sites may occur in immunocompromised hosts and contribute to morbidity (30,79). While knowledge of the biology of C. parvum has advanced in recent years, there are presently no consistently effective parasite-specific drugs, vaccines, or immunotherapies for cryptosporidiosis (7, 8, 11-13, 18, 19, 21, 22, 24, 32, 36, 37, 39, 40, 47, 51, 53, 57-59, 65-67, 69, 72, 75, 80, 81).Specific immune responses are known to prevent or terminate C. parvum infection in immunocompetent hosts (reviewed in reference 59). Therefore, passive immunization against C. parvum has been investigated for neonatal and immunocompromised hosts in which inadequate active immune responses predispose to infection and increase its duration and severity (reviewed in references 24 and 59). Early studies with animal models demonstrated that orally administered bovine colostral antibodies produced against whole C. parvum preparations can significantly reduce infection (28,29,55,56,60,76). Efficacy of polyclonal antibodies for passive immunotherapy of cryptosporidiosis in humans has also been demonstrated but was inconsistent among studies due largely to patient and treatment variables that complicated experimental designs and interpretation of results (24,48,50,59,77,78). Additionally, the efficacy of polyclonal antibody preparations produced against uncharacterized C. parvum antigens may have been limited by their heterogeneity and relatively low content of neutralizing antibodies (16,5...

show abstract

Hyperimmune bovine colostrum specific for recombinant Cryptosporidium parvum antigen confers partial protection against cryptosporidiosis in immunosuppressed adult mice

Cited by 60 publications

References 36 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

Cloning and Sequence Analysis of a Highly PolymorphicCryptosporidium parvumGene Encoding a 60-Kilodalton Glycoprotein and Characterization of Its 15- and 45-Kilodalton Zoite Surface Antigen Products

Efficacy of Monoclonal Antibodies against Defined Antigens for Passive Immunotherapy of Chronic Gastrointestinal Cryptosporidiosis

Contact Info

Product

Resources

About