Key to Schistosomiasis Vaccine

by Butantan Team

Published: October 26, 2021

The rhesus monkey, a species of primate that inhabits India, China and Afghanistan, and is also found in the monkey at the Butantan Institute, can help in the development of a vaccine against schistosomiasis, a parasitic disease that annually affects more than 200 million of people in the world. These are the conclusions of a study carried out by scientists from Butantan together with colleagues from Brazil, England, Holland and France; and showed that, by spontaneously curing themselves from schistosomiasis, rhesus monkeys are able to generate powerful antibodies against the parasites, being protected when they suffer a second infection. The research results are in the article “Rhesus macaques self-curing from a schistosome infection can display complete immunity to challenge”, published in the journal Nature Communications on Tuesday (26).

Scientific works from the 2000s already pointed out the rhesus monkey’s ability to naturally fight a first infection with Schistosoma mansoni, the causative agent of schistosomiasis, which is also called snail disease or water belly. Now, researchers Sergio Verjovski-Almeida and Murilo Sena Amaral, from the Butantan Parasitology Laboratory, along with other collaborators, have gone further and followed monkeys infected and reinfected with Schistosoma mansoni. The idea was to understand if, after exposure to a second attempt at infection, the monkeys’ immune memory worked and, thus, use this knowledge as a basis for the development of a possible vaccine.

In the first part of the research, twelve rhesus monkeys were each infected with 700 Schistosoma mansoni parasites and the infection was monitored by measuring a specific antigen of the parasite released into the monkey’s bloodstream. All monkeys healed between the 12th and 17th week. After 42 weeks, with the monkeys already free of the parasites, the scientists monitored the same indicator after a second infection. The conclusion was that monkeys recovered even faster from reinfection.

In fact, after the second infection, the monkeys did not show clinical symptoms of the disease (some monkeys had mild symptoms such as diarrhea and dehydration after the first infection) and already between the first and fourth weeks after reinfection, the schistosomes did not even mature until adult worms and did not release eggs.

At the end of the experiment, fewer than three worms (all stunted) were recovered from each monkey, which raised the hypothesis that antibodies to the rhesus somehow blocked the maturation and feeding of the parasites, which failed to develop. To test this hypothesis, the antibodies generated by the monkeys were incubated with parasites in the laboratory. This incubation led to the death of the parasites, and nine genes in the parasite’s autophagy pathway were identified as inhibited by the monkey’s immune defense.

The study gains importance given the environmental impact that has been reshaping the distribution of schistosomiasis, including increasing its incidence in the state of São Paulo. The parasites infect people who come into contact with contaminated water and settle inside the blood vessels of the intestine and liver, where the deposited eggs that cause the disease accumulate. As humans cannot eliminate the parasite naturally, the disease becomes dangerous because it causes serious complications in the affected organs.

The only drug to combat schistosomiasis recommended by the World Health Organization is Praziquantel, which is ineffective against young forms of the parasite and does not prevent reinfection. With no vaccine currently available to fight the disease, the next phases of the study will be identifying the parasite proteins that are targeted by monkey antibodies and testing these proteins as vaccine candidates in mice.

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