Immune effector responses to an excretory-secretory product of<i>Giardia lamblia</i>

Kaur, Hardeep; Samra, Hasan; Ghosh, Sujata; Vinayak, V. K.; Ganguly, Nirmal Kumar

doi:10.1111/j.1574-695x.1999.tb01228.x

Cited by 17 publications

(1 citation statement)

References 55 publications

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“…Multiple G. lamblia proteins are recognized by immune sera, but only a few have been identified at the molecular level or proven to be protective (18,27,28). Among the best-characterized antigens of G. lamblia are variant-specific surface proteins (VSPs) (29), whose functions remain poorly understood (30).…”

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Identification of Conserved Candidate Vaccine Antigens in the Surface Proteome of Giardia lamblia

et al. 2019

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Giardia lamblia, one of the most common protozoal infections of the human intestine, is an important worldwide cause of diarrheal disease, malabsorption, malnutrition, delayed cognitive development in children, and protracted postinfectious syndromes. Despite its medical importance, no human vaccine is available against giardiasis. A crude veterinary vaccine has been developed, and experimental vaccines based on expression of multiple variant-specific surface proteins have been reported, but poorly defined vaccine components and excessive antigen variability are problematic for pharmaceutical vaccine production. To expand the repertoire of antigen candidates for vaccines, we reasoned that surface proteins may provide an enriched source of such antigens since key host effectors, such as secretory IgA, can directly bind to such antigens in the intestinal lumen and interfere with epithelial attachment. Here, we have applied a proteomics approach to identify 23 novel surface antigens of G. lamblia that show Ͼ90% amino acid sequence identity between the two humanpathogenic genetic assemblages (A and B) of the parasite. Surface localization of a representative subset of these proteins was confirmed by immunostaining. Four selected proteins, uridine phosphorylase-like protein-1, protein 21.1 (GL50803_27925), ␣1-giardin, and ␣11-giardin, were subsequently produced in recombinant form and shown to be immunogenic in mice and G. lamblia-infected humans and confer protection against G. lamblia infection upon intranasal immunization in rodent models of giardiasis. These results demonstrate that identification of conserved surface antigens provides a powerful approach for overcoming a key rate-limiting step in the design and construction of an effective vaccine against giardiasis.

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Identification of Conserved Candidate Vaccine Antigens in the Surface Proteome of Giardia lamblia

et al. 2019

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Excreted/secreted glycoproteins of G. intestinalis play an essential role in the antibody response

Morelle

et al. 2006

Parasitol Res

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In the present work, glycoproteins in the excretory/secretory products of G. intestinalis were identified and the reactivity in serum of immunized mice with these molecules was evaluated by western blotting before and after chemical treatment or enzymatic deglycosylation. Glycoproteins of 58 and 63 kDa were revealed in E/S products after periodic acid-Schiff (PAS) stain. Studies of carbohydrate specificity using digoxigenin-labeled lectins, revealed the presence of O-glycans and N-glycans. Chemical treatment of excretory/secretory products with sodium meta-periodate or enzymatic deglycosylation with N-glycosidase F reduced the reactivity in serum for proteins of 36, 58 and 63 kDa, respectively. These results show the presence of glycoproteins in E/S products of G. intestinalis and suggest that the antibody response is directed against glycoepitopes. The expression of carbohydrate moieties in the E/S-G. intestinalis may play an essential role in the antibody response and may be a target for serodiagnosis or immune intervention in human giardiasis.

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Antibody and cytokine responses to Giardia excretory/secretory proteins in Giardia intestinalis-infected BALB/c mice

et al. 2014

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The humoral and cellular responses against excretory/secretory proteins and soluble extracts of Giardia intestinalis were evaluated in the course of experimental G. intestinalis infection in BALB/c mice. Production of IgG1, IgG2a, IgA, and IgE antibodies against excreted/secreted proteins and soluble extract was detected after infection by G. intestinalis. Specific IgA antibody against E/S proteins and soluble extract form intestinal fluids in infected mice was detected by ELISA. The Western blotting identified proteins of 30, 58, 63, and 83 kDa for IgA and IgG, respectively. High proliferation rate in vitro of spleen cell and secretion of interleukin-4 (IL-4) at 21 days p.i. after stimulation with excreted/secreted proteins and low proliferative response in the presence of soluble extract in infected BALB/c mice was observed. High production of interferon gamma (IFN-γ) and interleukin-5 (IL-5) at the time of decreasing cyst output (14-21 days p.i.) in infected mice was recorded, suggesting the important role of these cytokines in the control of the infection. Interestingly, progressive and gradual increase of the interleukin-10 after stimulation with both preparations was recorded from 7 days until 28 days after infection, indicating the possible regulatory effect of these antigens on the immune response during Giardia infection. Therefore, the infection by Giardia duodenalis stimulates a mixed response Th1 and Th2, mainly stimulated by excretory/secretory antigens. The immunogenicity of these antigens may be a suitable for identification of the proteins related with the effective immune response in the course of infection by G. duodenalsis.

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Immune effector responses to an excretory-secretory product ofGiardia lamblia

Cited by 17 publications

References 55 publications

Identification of Conserved Candidate Vaccine Antigens in the Surface Proteome of Giardia lamblia

Identification of Conserved Candidate Vaccine Antigens in the Surface Proteome of Giardia lamblia

Excreted/secreted glycoproteins of G. intestinalis play an essential role in the antibody response

Antibody and cytokine responses to Giardia excretory/secretory proteins in Giardia intestinalis-infected BALB/c mice

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