6 results on '"Pravetoni, M."'
Search Results
2. Co-administration of morphine and oxycodone vaccines reduces the distribution of 6-monoacetylmorphine and oxycodone to brain in rats
- Author
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Pravetoni, M., primary, Raleigh, M.D., additional, Le Naour, M., additional, Tucker, A.M., additional, Harmon, T.M., additional, Jones, J.M., additional, Birnbaum, A.K., additional, Portoghese, P.S., additional, and Pentel, P.R., additional
- Published
- 2012
- Full Text
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3. Pre-clinical safety and toxicology profile of a candidate vaccine to treat oxycodone use disorder.
- Author
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Hamid FA, Marker CL, Raleigh MD, Khaimraj A, Winston S, Pentel PR, and Pravetoni M
- Subjects
- Aluminum, Animals, Oxycodone therapeutic use, Rats, Rats, Sprague-Dawley, Vaccines, Conjugate, Drug Overdose, Opioid-Related Disorders drug therapy, Opioid-Related Disorders prevention & control
- Abstract
Opioid use disorders (OUD) and overdose represent a public health threat, resulting in thousands of deaths annually worldwide. Vaccines offer a promising treatment for OUD and potentially the prevention of fatal overdoses. The Oxy(Gly)
4 -sKLH Conjugate Vaccine, Adsorbed (Oxy(Gly)4 -sKLH) has shown promising pre-clinical efficacy at reducing the behavioral and pharmacological effects of oxycodone. To support its clinical evaluation, a GLP toxicology study was performed to address the safety of Oxy(Gly)4 -sKLH. Sprague Dawley rats were vaccinated with either aluminum adjuvant (alum) or vaccine adsorbed on alum. Low and high doses of Oxy(Gly)4 -sKLH, equivalent to a 1X or 47X human dose, respectively, were administered every two weeks for a total of four vaccinations. Both vaccine doses induced high antibody titers. Vaccine-related toxicity was assessed postmortem in one experimental group after receiving the fourth immunization of the vaccine's high dose. For the remaining experimental groups, rats were challenged with 1.5 mg/kg/day s.c. oxycodone for 7 days after the fourth vaccination to assess whether concurrent exposure to oxycodone in vaccinated animals resulted in toxicity. All rats, except a subset of the aluminum control and the high dose vaccine groups, were sacrificed following oxycodone exposure. These subsets were allowed a four weeks recovery period prior to euthanasia. In this study, no Oxy(Gly)4 -sKLH-related hematology, clinical chemistry, urinalysis, body weight, organ weight, or anatomic pathology toxicological findings were observed. These results demonstrate that the Oxy(Gly)4 -sKLH vaccine is well tolerated, is immunogenic even at low doses, and does not produce undesired side effects in rats., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Scott Winston reports a relationship with Winston Biopharmaceutical Consulting that includes: consulting or advising., (Copyright © 2022 Elsevier Ltd. All rights reserved.)- Published
- 2022
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4. Polymer-mediated delivery of vaccines to treat opioid use disorders and to reduce opioid-induced toxicity.
- Author
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Gradinati V, Baruffaldi F, Abbaraju S, Laudenbach M, Amin R, Gilger B, Velagaleti P, and Pravetoni M
- Subjects
- Analgesics, Opioid toxicity, Animals, Mice, Oxycodone therapeutic use, Polymers, Rats, Opioid-Related Disorders drug therapy, Vaccines therapeutic use
- Abstract
Vaccines offer a potential strategy to treat opioid use disorders (OUD) and to reduce the incidence of opioid-related overdoses. Vaccines induce opioid-specific polyclonal antibodies that selectively and effectively bind the target opioid and prevent its distribution across the blood-brain barrier. Because antibody-mediated reduction of drug distribution to the brain reduces drug-induced behavior and toxicity, vaccine efficacy depends on the quantity and quality of the antibody response. This study tested whether polymer-mediated delivery could improve vaccine efficacy against opioids as well as eliminate the need for booster injections normally required for a successful immunization. A series of novel biodegradable biocompatible thermogelling pentablock co-polymers were used to formulate a candidate vaccine against oxycodone in mice and rats. Polymer-based delivery of the anti-oxycodone vaccine was equally or more effective than administration in aluminum adjuvant in generating oxycodone-specific antibodies and in reducing oxycodone-induced effects and oxycodone distribution to the brain in mice and rats. The composition and release kinetics of the polymer formulations determined vaccine efficacy. Specifically, a formulation consisting of three simultaneous injections of the anti-oxycodone vaccine formulated in three different polymers with slow, intermediate, and fast release kinetics was more effective than an immunization regimen consisting of three sequential injections with the vaccine adsorbed on aluminum. The novel three-phased polymer vaccine formulation was effective in blocking oxycodone-induced antinociception, respiratory depression and bradycardia in rats., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Valeria Gradinati, Federico Baruffaldi, Santhi Abbaraju, Megan Laudenbach and Marco Pravetoni have no competing interests to declare. Rasidul Amin and Brian Gilger have financial interest in i-novion, Inc., and Poonam Velagaleti is a cofounder of i-novion, Inc., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2020
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5. Increased efficacy of a trivalent nicotine vaccine compared to a dose-matched monovalent vaccine when formulated with alum.
- Author
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de Villiers SH, Cornish KE, Troska AJ, Pravetoni M, and Pentel PR
- Subjects
- Alum Compounds administration & dosage, Animals, Injections, Intraperitoneal, Injections, Subcutaneous, Male, Models, Animal, Nicotine antagonists & inhibitors, Rats, Smoking immunology, Adjuvants, Immunologic administration & dosage, Nicotine immunology, Smoking therapy, Smoking Prevention, Vaccination methods, Vaccines administration & dosage, Vaccines immunology
- Abstract
Vaccination against nicotine is a potential treatment for tobacco smoking. Clinical trials show effect only in high antibody responders; therefore it is necessary to increase the effectiveness of nicotine vaccines. The use of a multivalent vaccine that activates several B cell populations is a possible approach to increase antibody response. The aim of this study was to investigate whether three different nicotine immunogens could be mixed to generate independent responses resulting in additive antibody titers, and whether this would alter nicotine distribution to a greater extent than antibodies generated by a monovalent vaccine. When immunogens were administered s.c. with alum adjuvant, the trivalent vaccine generated significantly higher titers and prevented the distribution of an i.v. nicotine dose to brain to a greater extent than an equivalent dose of a monovalent vaccine. The number of rats with antibody titers >1:10,000 was significantly increased in the trivalent group compared to the monovalent group. There were no correlations between the titers generated by the different nicotine immunogens in the trivalent vaccine, supporting the hypothesis that the immunogens generated independent responses from distinct populations of B cells. In contrast, when administered i.p. in Freund's adjuvant, the trivalent nicotine vaccine was not more immunogenic than its component monovalent vaccine. Vaccine immunogenicity was suppressed if unconjugated protein was added to the monovalent vaccine formulated in Freund's adjuvant, compared to monovalent vaccine alone. These data suggest a protein-protein interaction that affects titers negatively and is apparent when the vaccines are formulated with Freund's adjuvant. In summary, a trivalent nicotine vaccine formulated with alum showed significantly higher efficacy than a dose-matched monovalent vaccine and may offer a strategy for increasing nicotine vaccine immunogenicity. This approach may be generalizable to other nicotine immunogens or vaccines for other addictive drugs., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2013
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6. High immunogenicity of nicotine vaccines obtained by intradermal delivery with safe adjuvants.
- Author
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Chen X, Pravetoni M, Bhayana B, Pentel PR, and Wu MX
- Subjects
- Animals, Immunotherapy, Male, Mice, Mice, Inbred BALB C, Tobacco Use Disorder therapy, Adjuvants, Immunologic administration & dosage, Nicotine immunology, Vaccines immunology
- Abstract
Immunotherapy for tobacco addiction may offer a safe, alternative treatment if the immunogenicity of the current nicotine vaccines can be improved. We show here that intradermal (ID) immunization induces the production of antibody directed against nicotine (NicAb) at a much higher level than conventional intramuscular (IM) immunization. The magnitude and duration of NicAb production was further increased robustly by non-inflammatory laser vaccine adjuvant (LVA), slightly inflammatory monophosphoryl lipid A (MPL) or a combination of MPL and CpG adjuvants. Consequently, significantly fewer vaccination doses were required to attain a high level of NicAb production for an extended period of time and reduce nicotine entry into the brain in the presence of LVA, MPL or MPL/CpG adjuvant, respectively. Yet, the potency of these adjuvants to augment ID nicotine vaccine immunogenicity came at the expense of local skin reactogenicity, with LVA causing little skin reaction and MPL/CpG stimulating overt skin irritation. These observations underscore a necessity of a balance between optimal adjuvant potency and undesired local reactogenicity. In summary, our study presents a novel approach to significantly improve nicotine vaccine immunogenicity by a combination of safe cutaneous vaccine adjuvants with ID immunization., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
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