CRUZIVAX: Developing a Prophylactic and Therapeutic Vaccine Against Chagas Disease

A team of CONICET specialists was awarded the 2023 César Milstein Prize for Research in Biotechnology with an Impact on Health, awarded by CONICET and the Pablo Cassará Foundation, for a project to develop a prophylactic and therapeutic vaccine against the disease. of Chagas. The project, called CRUZIVAX, has significant funding from the European Economic Community, which allocated 8.4 million euros, and in addition to its Argentine support, it includes the collaboration of ten research groups from seven European countries.

“It is very important to develop a vaccine against Chagas disease from Argentina, because since it is a very forgotten disease, because it is practically limited to Latin America and mainly affects the poor, there are no companies that are willing to invest the money that is needed. for its development, because it may not provide sufficient benefits. So, if we don’t take care of it, probably no one will take care of it,” indicates Emilio Malchiodi, project leader, CONICET researcher and director of the Institute for Humoral Immunity Studies Prof. Dr. Ricardo A. Margni (IDEHU, CONICET-UBA ), and then adds that in Argentina it is estimated that there are 1.3 million infected people and about a thousand babies per year contract the infection through the maternal-fetal route.

Chagas disease is caused by the parasite Trypanosoma cruziwhose infection is transmitted mainly through the Triatoma infestans, an insect commonly known as vinchuca that feeds on the blood of wild, domestic mammals and humans. In addition to the vector route, the infection can also be transmitted through blood and organ donations, from mothers to children (congenital route) and through the ingestion of food contaminated by the parasite. Currently it is estimated that between 7 and 10 million people in the world are infected by T. cruzi, the vast majority of which are concentrated in endemic areas of twenty-one Latin American countries, including an area of ​​Argentina that extends from the center to the north of the country, where it has its highest incidence. It is estimated that this pathology has about 56 thousand new cases in the world each year and produces more than 10 thousand deaths. It is also estimated that around 100 million people around the world are at risk of infection and that annually around 9,000 babies inherit the disease from their mothers.

Currently, and for decades, Chagas disease can be treated with the drugs benznidazole and nifurtimox. Although these drugs are very effective in eliminating the parasite at the beginning of the infection (acute stage), their effectiveness decreases in the next phase (chronic stage) – which is when most infections are diagnosed -, in which the T. cruzi It is already sheltered in the muscle tissues and not so exposed to the action of drugs. Although in chronic patients, antiparasitic treatment can slow the progression of the disease and prevent transmission from mother to child, about a third of these patients present cardiac disorders and ten percent, digestive, neurological or combined disorders. To date, there are no approved vaccines to prevent infection or treat it.

Malchiodi’s team at IDEHU and at the Institute for Research in Microbiology and Medical Parasitology (IMPaM, CONICET-UBA) has been accumulating experience for two decades in the search to develop a vaccine against Chagas disease, which would prevent both new infections occur, such as treating people who live with the parasite.

CRUZIVAX had its starting point in June 2019 and was shortly interrupted by the COVID-19 pandemic and the consequent isolation and social distancing measures. However, given the state of progress, Malchiodi hopes that the developed vaccine formulation can begin to be tested in humans within the next two years.

The project currently underway includes the entire preclinical stage and the first phase (phase 1) of clinical trials in humans. The preclinical stage ranges from the development and production of the antigen and the adjuvant, with a quality that meets the standards of good laboratory practices (GLP) and good manufacturing practices (GMP). in English), until its testing in three animal species: mice, dogs and monkeys. Added to this are toxicity studies in other animal models and the development of the formulation that will be tested in humans once regulatory entities authorize clinical trials.

The antigen used by this vaccine candidate has original characteristics. “To develop the antigen we use in this vaccine, we take portions of three proteins from T. cruzi and we combine them into a single molecule, what is known as a chimeric antigen. The three proteins we use are very important for the parasite and individually they can protect against infection, so combining them allows us to attack the pathogen in three different places, which gives it less chance of survival,” says Malchiodi, who is also a full professor. of Immunology in Immunology at the Faculty of Pharmacy and Biochemistry of the University of Buenos Aires (UBA).

The chimeric antigen, called Traspain, was developed by genetic engineering in the laboratory directed by Malchiodi at the IDEHU and the IMPaM, and is patented by the CONICET and the UBA. According to Malchiodi, generating a molecule in which the three antigens are combined is 33 percent cheaper than adding the three proteins separately in the same vaccine.

The vaccine is also composed of a latest generation adjuvant, cyclic di-adenosine monophosphate (CDA), whose action on the mucous membranes facilitates the nasal administration of the vaccine, which consists of a spray. “We wanted to develop a vaccine for nasal application, because the studies we carried out show that this favors its acceptance compared to what happens with the injectable route. Generally people prefer not to be punctured,” says the researcher.

At this time, the vaccine candidate has already been successfully tested in mice and is being analyzed in monkeys and dogs.

2023-09-28 22:23:19
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