Research Article: An Oral Recombinant Vaccine in Dogs against Echinococcus granulosus, the Causative Agent of Human Hydatid Disease: A Pilot Study

Date Published: January 16, 2008

Publisher: Public Library of Science

Author(s): Anne-Francoise Petavy, Carlos Hormaeche, Samia Lahmar, Hammou Ouhelli, Alejandro Chabalgoity, Thierry Marchal, Samira Azzouz, Fernanda Schreiber, Gabriela Alvite, Marie-Elisabeth Sarciron, Duncan Maskell, Adriana Esteves, Georges Bosquet, Ricardo Fujiwara

Abstract: Dogs are the main source of human cystic echinococcosis. An oral vaccine would be an important contribution to control programs in endemic countries. We conducted two parallel experimental trials in Morocco and Tunisia of a new oral vaccine candidate against Echinococcus granulosus in 28 dogs. The vaccine was prepared using two recombinant proteins from adult worms, a tropomyosin (EgTrp) and a fibrillar protein similar to paramyosin (EgA31), cloned and expressed in a live attenuated strain of Salmonella enterica serovar typhimurium.In each country, five dogs were vaccinated with the associated EgA31 and EgTrp; three dogs received only the vector Salmonella; and six dogs were used as different controls. The vaccinated dogs received two oral doses of the vaccine 21 d apart, and were challenged 20 d later with 75,000 living protoscoleces. The controls were challenged under the same conditions. All dogs were sacrificed 26–29 d postchallenge, before the appearance of eggs, for safety reasons.We studied the histological responses to both the vaccine and control at the level of the duodenum, the natural localization of the cestode. Here we show a significant decrease of parasite burden in vaccinated dogs (70% to 80%) and a slower development rate in all remaining worms. The Salmonella vaccine EgA31-EgTrp demonstrated a high efficacy against E. granulosus promoting its potential role in reducing transmission to humans and animals.

Partial Text: Cystic echinococcosis, also called hydatidosis, represents a severe public health and livestock problem, particularly in developing countries [1]–[3]. The causative agent is the cestode Echinococcus granulosus. The adult stage may be found in the small intestine of canine carnivores. Growth of the larval stage throughout the internal organs, especially the liver and lungs, causes clinical signs in the intermediate hosts, such as sheep, cattle, and camels. Humans may also become host to this metacestode. Usually, however, intermediate hosts become infected by grazing on vegetation contaminated by eggs shed by adult worms via canine feces [4].

To our knowledge, this is the first report of protection induced in dogs against the adult stage of E. granulosus after oral vaccination with a recombinant parasite protein. We have demonstrated the efficacy of the vaccine in two separate trials, each in a different country. Vaccination caused a decrease of more than 70% in the number of cestodes, and of a slower development rate of those recovered from vaccinated animals. Suppression of cestode development has also been observed recently [38] following the injection of a vaccine composed of recombinant EgM proteins. Out of consideration of the risk of infection to technical staff working with the patent infection in the dogs, we chose not to estimate the number of eggs in gravid segments, notwithstanding the opportunity offered by the strong expression of EgA31 in eggs and its potential usefulness as a marker [11]. We have demonstrated that a field vaccine based on this technology could be formulated into baits to target domestic and stray dogs in endemic countries.



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