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 ...