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It was a long work, but the result compensated it. After nearly 30 years of study, Brazil is about to begin testing the human rheumatoid arthritis vaccine, an autoimmune disease that causes heart problems in an estimated 15 million children each year worldwide. It was developed by the rheumatic fever research group of the Immunology Laboratory of the Institute of Cardiology (Incor) Hospital Clinic of the Faculty of Medicine of the University from São Paulo (USP)
According to team coordinator, Luiza Guilherme Guglielmi, the disease affects children and adolescents aged 5 to 18 years and genetically predisposed to Streptococcus pyogenes.
"It starts after an infection of the throat, especially with fever," he says. At first, it can cause arthritis (joint pain), which usually disappears in a very short time.
"However, if untreated, carriers of susceptibility genes may have as sequelae cardiac rheumatic disease (CKD), which damages heart valves, glomerulonephritis (kidneys) and Sydenham's chorea. (Central Nervous System). "
Heart Problems
The DRC affects the pericardium (the membrane that surrounds the body). heart), the myocardium (muscular organ) and the endocardium (the membrane lining the interior of the myocardium and limits the cardiac cavities), which can cause progressive and permanent lesions, triggering heart failure, requiring surgery
"Pericarditis and Myocarditis have a good prognosis with resolution within 30 days of infection," says Luiza. "Although endocarditis causes valvular lesions, especially mitral and aortic valves, which can lead to heart failure."
Although severe, these sequelae affect only 3% to 5% of those infected. Nevertheless, the absolute numbers are high, with about 30,000 new cases per year in Brazil. Of these, approximately 30% may require cardiac surgery, making it one of the most costly diseases for the public health system
. In other cases, Streptococcus pyogenes only causes inflammation of the throat, which can be easily treated with antibiotics. like penicillin or benzathine. The problem is that in many undeveloped countries, these drugs are not available to everyone. Therefore, rheumatic fever is also considered a disease related to the socio-economic conditions of a region or country
. In children and adolescents who are sensitive to the bacteria, the infection triggers an autoimmune reaction in the body. In other words, the immune system, in addition to attacking the microorganism, also turns against the cells of the person, in the case of the heart itself.
According to Luiza, this is because a membrane protein of S. pyogenes called M, is very similar to those of the heart, joints and the central nervous system of the human being. This confuses the body's defenses, which begin to attack not only the bacteria, but also the healthy tissues of the heart organ. The bacteria can even be eliminated, but the antibodies "believe" that she is still there and continue the war, now against whom they must defend themselves.
Thirty Years of Studies
The vaccine aims to stop this process by ending the undue conflict, technically known as cross-reaction. The work that led to its development began in 1988 with the detailed study of rheumatic fever, its causes and effects. The first scientific article of Luiza's group was published in the American magazine Circulation in 1991 and had a significant impact on international scientific knowledge.
"He opened the possibility to several other publications of our group on the disease," says the researcher. . "The knowledge gained led us to develop an immunizing agent to prevent it."
The idea was to create a product that would allow the human immune system to produce large amounts of specific antibodies against the bacterium S. pyogenes, that they did not attack at all. 39, organism itself, in this case in the heart.
"It was a big challenge," remembers Luiza. "The established design for the creation of the vaccine from synthetic peptides (protein parts) required considerable work over a two-year period."
The next step consisted of preclinical trials on experimental models. of normal and transgenic mice (human leukocyte antigen (HLA) molecules responsible for triggering the immune response
"We then obtained funding from the National Development Bank (BNDES)), for the point of the product, in collaboration with the Butantan Institute, "says Luiza.
Called StreptinC-A streptococcal vaccine, the immunizer was subjected to several tests on mice, with its formulation in aluminum hydroxide (adjuvant, or substance enhancing action). 39, a drug) in three doses: 50, 100 and 200 micrograms / ml, and in small pigs, between 20 and 30 kg (plus or minus the weight of a child), which, from a biological point of view , are similar to the man. In this case, the animals were accompanied by an echocardiogram as a safety test.
In rodents, large amounts of the S. pyogenes bacteria were injected, which could kill them. In the case of pigs, immune to rheumatic fever, the purpose of the infection was to create an abscess.
"All results indicated effective immunization (80% of vaccinated mice survived), producing high levels of antibodies against the microorganism and without cross-reactivity," explains Luiza.
"This shows that there is a high probability that the product induces good protection in humans without causing adverse reactions or autoimmune diseases."
with him, many countries , especially in Africa, but also developed countries, such as Australia and the United States, are waiting for this vaccine against rheumatic fever.
"The World Health Organization itself is waiting for its production," he says. "But this is no longer ours.It has already been approved by the National Commission for Ethics and Research (CONEP), but it is still being registered with the l & # 39; Brazilian National Health Surveillance Agency (Anvisa), two Brazilian regulatory agencies, for clinical trials. "
When this occurs, tests are performed on 48 healthy subjects, divided into four groups of 12. One will receive a placebo, and three other different doses of the immunizing vaccine (50 100 and 200 micrograms / ml).
"Hopefully, Brazil will be highlighted, as the country that contributes most to the knowledge of rheumatic fever and its control," Luiza said. "In addition, our product could serve as a model for the development of vaccines against other autoimmune diseases."
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