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

Augusto, Paulo Sérgio de Almeida; Pereira, Raissa Lima Gonçalves; Caligiorne, Sordaini Maria; Sabato, Brian; Assis, Bruna Rodrigues Dias; Santo, Larissa Pires do Espírito; Reis, Karine Dias dos; Goulart, Gisele Assis Castro; Fátima, Ângelo de; Neves, Maila de Castro Lourenço das; Garcia, Fernando Coutinho

doi:10.1038/s41380-021-01210-1

Cited by 4 publications

(5 citation statements)

References 44 publications

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“…In 2021, de Almeida Augusto et al were the first to report the efficacy of an anti-cocaine vaccine in pregnant rodents (Table 1). 50 Here, GNE-KLH vaccination produced and maintained anti-cocaine IgG (polyclonal) antibody responses and avidity during pregnancy, protecting pregnant rats and their pups against prenatal cocaine damage during pregnancy until weaning. This research represented important evidence for the efficacy of an innovative mechanism to prevent prenatal cocaine exposure damage and has underpinned the foundation for anti- cocaine vaccine research in pregnant women who suffer from cocaine substance abuse.…”

Section: Pre-clinical Advances Inmentioning

confidence: 99%

Anti-cocaine Vaccine Development: Where Are We Now and Where Are We Going?

Stephenson

Tóth

2023

J. Med. Chem.

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Cocaine is one of the oldest and most widely used illicit drugs in the world and is responsible for major worldwide medical and social problems. Drug addiction is a disease state where the body relies on a substance for normal functioning and develops a physical dependence leading to compulsive and repetitive use despite negative consequences to the user's health, mental state, or social life. The primary driver for the development of anti-cocaine vaccines has been the failure to develop effective pharmacological treatments to combat cocaine dependence. Despite several decades of research, no approved pharmacological treatments for cocaine dependence are available to assist addicts to overcome cocaine withdrawal or to prevent drug relapse. This Perspective highlights the challenges associated with anti-cocaine vaccines, including the current state of anti-cocaine vaccines and catalytic antibody research to aid in the fight against cocaine addiction.

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Section: Pre-clinical Advances Inmentioning

confidence: 99%

Anti-cocaine Vaccine Development: Where Are We Now and Where Are We Going?

Stephenson

Tóth

2023

J. Med. Chem.

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“…The use of carrier proteins and adjuvants presents a number of unfavorable properties on these formulations, including ineffective boosting, lack of pharmaceutical reproducibility between hapten and protein conjugation leading to a variable haptenation ratio, and potential toxic effects from experimental adjuvants. − Further, some of the most common and promising protein carriers have the potential to be ineffective, leading to reduced effectiveness during boosting due to carrier-induced epitope suppression . This phenomenon has been caused by carrier-specific antibodies induced by childhood immunization or from pre-existing infection with organisms from which common carriers are derived (e.g., Schistosoma mansoni). ,− Although one cocaine vaccine has progressed to phase III clinical trials showing promising efficacy, this effect was only observed in a small percentage of participants where it is hypothesized to be associated with major histocompatibility complex (MHC) class II polymorphism and the lack of effective T helper involvement …”

Section: Introductionmentioning

confidence: 99%

“…Previously reported cocaine vaccines have consisted of a small drug-like hapten conjugated to a large immunogenic carrier protein delivered with an adjuvant. − The synthetic chemistry and structure stability versus immunogenicity of cocaine hapten variations have been extensively explored; , however, the investigation hapten delivery has been limited to conjugation to different immunogenic proteins formulated with an adjuvant(s) . The use of carrier proteins and adjuvants presents a number of unfavorable properties on these formulations, including ineffective boosting, lack of pharmaceutical reproducibility between hapten and protein conjugation leading to a variable haptenation ratio, and potential toxic effects from experimental adjuvants. − Further, some of the most common and promising protein carriers have the potential to be ineffective, leading to reduced effectiveness during boosting due to carrier-induced epitope suppression .…”

Section: Introductionmentioning

confidence: 99%

Synthetic Anti-Cocaine Nanoaccine Successfully Prevents Cocaine-Induced Hyperlocomotion

Madge,

Alexander,

Azuar

et al. 2023

J. Med. Chem.

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Cocaine is one of the most widely used and increasingly popular illicit psychoactive drugs. Unlike other commonly used substances of abuse, cocaine has no pharmacological therapies to treat addiction or aid in rehabilitation. Immunopharmacology has long been touted as a possible avenue to develop effective anticocaine therapies; however, lack of efficacy and designs which are not consistent with simple large-scale production have hindered vaccine translation. We have designed and synthesized a peptide-based anti-cocaine immunogen which we have shown is capable of inducing physiologically relevant immune responses in mice as part of a self-adjuvanting delivery system or in combination with the human-approved commercial adjuvant MF59. We have demonstrated that immunization with the reported vaccine elicits high titers of anti-cocaine IgG and prevents cocaine-induced hyperlocomotion in an in vivo murine model. This peptide-hapten immunogen along with self-adjuvanting liposomal-based delivery system provides a platform for the development of effective anti-drug vaccines.

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“…Of these three components, cocaine hapten design appears optimized, with GNE being the hapten of choice (Figure A) . In short, GNE has been shown to elicit a strong and long-lasting immune response mainly due to its superior serum stability in comparison to other cocaine haptens examined over the past two decades and is currently being utilized in the dAd5GNE clinical trial . In contrast, there is vast room for adjuvant optimization not only for cocaine but other drugs of abuse vaccines, given the limited number of adjuvants licensed by the FDA, which include aluminum salts, oil-in-water emulsion, AS04, AS01, and CpG ODN. , …”

Section: Introductionmentioning

confidence: 99%

“…6 In short, GNE has been shown to elicit a strong and long-lasting immune response mainly due to its superior serum stability in comparison to other cocaine haptens examined over the past two decades and is currently being utilized in the dAd5GNE clinical trial. 7 In contrast, there is vast room for adjuvant optimization not only for cocaine but other drugs of abuse vaccines, given the limited number of adjuvants licensed by the FDA, which include aluminum salts, oil-in-water emulsion, AS04, AS01, and CpG ODN. 8,9 As described, vide supra, only a small swath of adjuvants have been approved for human use, and despite the undeniable challenges of getting a new adjuvant approved, a variety of adjuvants have been assessed in the field of drugs of abuse vaccines including alum (alhydrogel)/CpG formulations, lipid analogues such as MPLA and GLA-SE, inulin-based systems, and TLR3 agonist dsDNA/PLGA nanoparticles.…”

Section: ■ Introductionmentioning

confidence: 99%

Polyphosphazene: A New Adjuvant Platform for Cocaine Vaccine Development

et al. 2022

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Cocaine is a highly addictive drug that has seen a steady uptrend causing severe health problems worldwide. Currently, there are no approved therapeutics for treating cocaine use disorder; hence, there is an urgent need to identify new medications. Immunopharmacotherapeutics is a promising approach utilizing endogenous antibodies generated through active vaccination, and if properly programmed, can blunt a drug’s psychoactive and addictive effects. However, drug vaccine efficacy has largely been limited by the modest levels of antibodies induced. Herein, we explored an adjuvant system consisting of a polyphosphazene macromolecule, specifically poly[di(carboxylatoethylphenoxy)-phosphazene] (PCEP), a biocompatible synthetic polymer that was solicited for improved cocaine conjugate vaccine delivery performance. Our results demonstrated PCEP’s superior assembling efficiency with a cocaine hapten as well as with the combined adjuvant CpG oligodeoxynucleotide (ODN). Importantly, this combination led to a higher titer response, balanced immunity, successful sequestering of cocaine in the blood, and a reduction in the drug in the brain. Moreover, a PCEP–cocaine conjugate vaccine was also found to function well via intranasal administration, where its efficacy was demonstrated through the antibody titer, affinity, mucosal IgA production, and a reduction in cocaine’s locomotor activity. Overall, a comprehensive evaluation of PCEP integrated within a cocaine vaccine established an advance in the use of synthetic adjuvants in the drugs of abuse vaccine field.

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

Cited by 4 publications

References 44 publications

Anti-cocaine Vaccine Development: Where Are We Now and Where Are We Going?

Anti-cocaine Vaccine Development: Where Are We Now and Where Are We Going?

Synthetic Anti-Cocaine Nanoaccine Successfully Prevents Cocaine-Induced Hyperlocomotion

Polyphosphazene: A New Adjuvant Platform for Cocaine Vaccine Development

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