Avaliação da eficácia da vacina UFMG-VAC-V4N2 na proteção materno-fetal à exposição à cocaína no período gestacional e perinatal

Abstract

Cocaine addiction is a worldwide public health problem for which there is no specific treatment available. New therapeutic proposals are being developed aiming at treatment through stimulation of the immune system, inducing the production of specific antibodies for cocaine. A new application of this therapeutic strategy is the prevention of intrauterine drug exposure. This strategy proved to be effective with the GNE-KLH vaccine. Thus, this work aimed to evaluate the effectiveness of active immunization with UFMG-VAC-V4N2 in pregnant rats, in maternal-fetal protection from prenatal exposure to cocaine. The study compared the vaccine with its placebo in adult rats of reproductive age. These were inoculated with 300 μL of the vaccine formulation with UFMG-V4N2 or its placebo, on days 0, 7, 21, 28 and 42, intramuscularly. On day 28 the rats were mated and mating confirmed by vaginal plug formation. From confirmation of mating, each rat received a daily dose of 20 mg/kg of cocaine solution, until delivery, intraperitoneally. Weight gain, duration of gestation, maternal water and food intake, maternal mortality, litter size and pup weight after weaning were evaluated. The dosage of IgG anti-cocaine antibodies in the serum of mothers and puppies and in breast milk was performed using the ELISA method. The open field test evaluated the acute effect on cocaine-induced hyperlocomotion in dams during pregnancy and in pups after weaning. The results showed that active immunization with the UFMG- VAC-V4N2 vaccine did not induce the production of anti-cocaine IgG antibodies in rats before and during pregnancy and in a dependent manner, these antibodies were also not quantified in the offspring of vaccinated rats and in breast milk . No statistical differences were observed for the variables evaluated in gestational and postnatal outcomes between the treated and placebo groups, as well as cocaine-induced hyperlomotor effects. After reviewing the entire method used, the nuclear magnetic resonance of the molecule used in the research pointed out points of degradation of the lot of the molecule used in the formulation. These results suggest that the UFMG- V4N2 molecule still requires more specific studies regarding its stability, which directly impacts the efficacy and safety of the vaccine formulation. Thus, forced degradation studies and the development of an analytical method that indicates stability are the next essential steps for UFMG-VAC-V4N2 to advance in the regulatory chain of pre- clinical and clinical studies.