Efficacy of a Gal-lectin subunit vaccine against experimental Entamoeba histolytica infection and colitis in baboons (Papio sp.)

Alla, Mohamed D. Abd; Wolf, Roman F.; White, Gary L.; Kosanke, Stanley D.; Cary, David; Verweij, Jaco J.; Zhang, Mie-Jie; Ravdin, Jonathan I.

doi:10.1016/j.vaccine.2012.02.066

Cited by 33 publications

(23 citation statements)

References 43 publications

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“…Toward this goal, a number of potential vaccine antigens have been partially validated, including the serine-rich E. histolytica protein (SREHP), a lipoproteophosphoglycan, a 29-kDa cysteine-rich thiol-dependent peroxidase, and a D-galactose/N-acetyl-D-galactosamine-specific amebic adherence lectin (Gal lectin) (11)(12)(13)(14)(15)(16). Each of these antigens is protective in rodent liver abscess models, and Gal lectin-based subunit vaccines protect against colitis in both mice and baboons (15,17). Protective immunity in children naturally infected with E. histolytica correlates with secretory IgA antibodies directed to the Gal lectin, further demonstrating its potential as a vaccine antigen (8, 9).…”

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confidence: 99%

Immunization with the Entamoeba histolytica Surface Metalloprotease EhMSP-1 Protects Hamsters from Amebic Liver Abscess

et al. 2015

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Diarrhea and amebic liver abscesses due to invasive Entamoeba histolytica infections are an important cause of morbidity and mortality in the developing world. Entamoeba histolytica adherence and cell migration, two phenotypes linked to virulence, are both aberrant in trophozoites deficient in the metallosurface protease EhMSP-1, which is a homologue of the Leishmania vaccine candidate leishmanolysin (GP63). We examined the potential of EhMSP-1 for use as a vaccine antigen to protect against amebic liver abscesses. First, existing serum samples from South Africans naturally infected with E. histolytica were examined by enzyme-linked immunosorbent assay (ELISA) for the presence of EhMSP-1-specific IgG. Nine of 12 (75%) people with anti-E. histolytica IgG also had EhMSP-1-specific IgG antibodies. We next used a hamster model of amebic liver abscess to determine the effect of immunization with a mixture of four recombinant EhMSP-1 protein fragments. EhMSP-1 immunization stimulated a robust IgG antibody response. Furthermore, EhMSP-1 immunization of hamsters reduced development of severe amebic liver abscesses following intrahepatic injection of E. histolytica by a combined rate of 68% in two independent animal experiments. Purified IgG from immunized compared to control animals bound to the surface of E. histolytica trophozoites and accelerated amebic lysis via activation of the classical complement cascade. We concluded that EhMSP-1 is a promising antigen that warrants further study to determine its full potential as a target for therapy and/or prevention of invasive amebiasis. Infectious diarrhea is the second most common cause of death in children under 5 years of age (1). Entamoeba histolytica, the enteric ameba that causes invasive amebiasis, was the most common intestinal parasite identified in children between 2 and 5 years of age in a recent comprehensive study of the causes of life-threatening diarrhea in children in sub-Saharan Africa and the Indian subcontinent (2). While amebiasis is still a significant problem in the first 2 years of life (2), the presence of E. histolytica-specific secretory IgA (sIgA) in breast milk correlates with a reduced risk of amebiasis in breastfeeding infants (3). The true global burden of E. histolytica infection remains unknown, but the frequency of infection can be staggering in areas of endemicity. In the Mirpur region of Dhaka, Bangladesh, greater than 50% of children have serologic evidence of E. histolytica infection by 5 years of age (4), and E. histolytica is the intestinal protozoan most frequently associated with diarrhea in this population (5). Invasive disease is characterized by dysentery and the potential for spread via the portal venous circulation to cause amebic liver abscesses (ALAs), which occur in approximately 1% of symptomatic cases (6).An effective E. histolytica vaccine could conceivably enable global eradication, since E. histolytica infects only humans and some higher nonhuman primates (7). There is currently no such vaccine, but some children with ...

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Immunization with the Entamoeba histolytica Surface Metalloprotease EhMSP-1 Protects Hamsters from Amebic Liver Abscess

et al. 2015

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“…Anti-lectin IgA response, however, was shown to be associated with protection from E. histolytica colonization in children [16]. A correlation has also been shown between IgA production and clearance of parasites in baboons [44]. In short, GLA-3M-052 liposome generated a robust anti-amebic mucosal IgA response that was protective in vitro .…”

Section: Discussionmentioning

confidence: 99%

Nanoformulation of synergistic TLR ligands to enhance vaccination against Entamoeba histolytica

Abhyankar

Noor

Tomai

et al. 2017

Vaccine

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Diarrheal infectious diseases represent a major cause of global morbidity and mortality. There is an urgent need for vaccines against diarrheal pathogens, especially parasites. Modern subunit vaccines rely on combining a highly purified antigen with an adjuvant to increase their efficacy. In the present study, we evaluated the ability of a nanoliposome adjuvant system to trigger a strong mucosal immune response to the Entamoeba histolytica Gal/GalNAc lectin LecA antigen. CBA/J mice were immunized with alum, emulsion or liposome based formulations containing synthetic TLR agonists. A liposome formulation containing TLR4 and TLR7/8 agonists was selected based on its ability to generate intestinal IgA, plasma IgG2a/IgG1, IFN-γ and IL-17A. Immunization with a mucosal prime followed by a parenteral boost generated a high mucosal IgA response that inhibited adherence of parasites to mammalian cells. Inclusion of the immune potentiator all-trans retinoic acid in the regimen further improved the mucosal IgA response. Immunization protected from infection with up to 55% efficacy. Our results show that a nanoliposome delivery system coupled to TLR agonists is a promising prospect for the development of vaccines against enteric pathogens, especially when a multifaceted immune response is desired.

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“…The heavy chain of Gal/GalNAc lectin contains the carbohydrate recognition domain (CRD) that is responsible for binding. In both mice and baboons vaccinated against E. histolytica , IgA antibodies against Gal/GalNAc lectin correlated with protection [16], [17]. In a cohort of preschool children in Dhaka, Bangladesh, mucosal IgA directed at the CRD domain was associated with protection of children from E. histolytica infection and disease.…”

Section: Adaptive Immunity: Mucosal Immunoglobulin a And Cell-mediatementioning

confidence: 96%

Host Immune Response to Intestinal Amebiasis

2013

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Efficacy of a Gal-lectin subunit vaccine against experimental Entamoeba histolytica infection and colitis in baboons (Papio sp.)

Cited by 33 publications

References 43 publications

Immunization with the Entamoeba histolytica Surface Metalloprotease EhMSP-1 Protects Hamsters from Amebic Liver Abscess

Immunization with the Entamoeba histolytica Surface Metalloprotease EhMSP-1 Protects Hamsters from Amebic Liver Abscess

Nanoformulation of synergistic TLR ligands to enhance vaccination against Entamoeba histolytica

Host Immune Response to Intestinal Amebiasis

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