Safety and immunogenicity of the anti-cocaine vaccine UFMG-VAC-V4N2 in a non-human primate model.

A promising strategy for cocaine addiction treatment is the anti-drug vaccine. These vaccines induce the production of anticocaine antibodies, capable of linking to cocaine, and decrease the passage of cocaine throughout the blood-brain barrier, decreasing drug activity in the brain. Our research group developed a new vaccine candidate, the UFMG-V4N2, to treat cocaine use disorders (CUD) using an innovative carrier based on calixarenes. This study assessed the safety and immunogenicity of the anti-cocaine vaccine UFMG-VAC-V4N2 in a non-human primate toxicity study using single and multiple vaccine doses. The UFMG-VAC-V4N2 yielded only mild effects in the injection site and did not influence the general health, feeding behavior, or hematological, renal, hepatic, or metabolic parameters in the vaccinated marmosets. The anti-cocaine vaccine UFMG-VAC-V4N2 presented a favorable safety profile and induced the expected immune response in a non-human primate model of Callithrix penicillata. This preclinical UFMG-VAC-V4N2 study responds to the criteria required by international regulatory agencies contributing to future anticocaine clinical trials of this anti-cocaine vaccine.

The GNE-KLH anti-cocaine vaccine protects dams and offspring from cocaine-induced effects during the prenatal and lactating periods.

Protecting children from prenatal cocaine exposure is a significant challenge for physicians and childbearing women with cocaine use disorder. Cocaine use is highly prevalent among reproductive-aged women and prenatal cocaine exposure produces obstetric, foetal neurodevelopmental and long-term behavioural impairments. Cocaine crosses the maternal and foetal blood-brain barrier and the placenta by diffusion. The best approach to prevent prenatal cocaine exposure is to stop cocaine use. However, only 25% of cocaine users can discontinue their use during pregnancy. Anti-cocaine vaccination decreases cocaine passage through the blood-brain barrier. This study describes an innovative approach for preventing prenatal cocaine exposure using the GNE-KLH anti-cocaine vaccine, a novel use for the named anti-drug vaccines. Here, we show that anti-cocaine vaccination with GNE-KLH produced and maintained anti-cocaine IgG antibody titres and avidity during pregnancy. These antibodies protected the pregnant rats and their pups against prenatal cocaine damage during pregnancy until weaning. The present work is the first preclinical evidence of the efficacy of an innovative mechanism to prevent prenatal cocaine exposure damage, a worldwide public health care issue. In the future, this mechanism may be useful in pregnant women with cocaine use disorder. Further studies to understand the mechanisms of how anti-cocaine antibodies exert their protective effects in pregnancy are warranted.