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Probing the effects of hapten stability on cocaine vaccine immunogenicity

Academic Article
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Overview

related to degree

  • Moreno, Amira, Ph.D. in Chemistry, Scripps Research 2006 - 2012

authors

  • Cai, X.
  • Whitfield, T.
  • Moreno, Amira
  • Grant, Y.
  • Hixon, M. S.
  • Koob, George
  • Janda, Kim

publication date

  • 2013

journal

  • Molecular Pharmaceutics  Journal

abstract

  • Judicious hapten design has been shown to be of importance when trying to generate a viable vaccine against a drug of abuse. Hapten design has typically been predicated upon faithfully emulating the unique chemical architecture that each drug presents. However, the need for drug-hapten congruency may also compromise vaccine immunogenicity if the drug-hapten conjugate possesses chemical epitope instability. There has been no systematic study on the impact of hapten stability as it relates to vaccine immunogenicity. As a starting point, we have probed the stability of a series of cocaine haptens through varying several of its structural elements, including functionality at the C2-position, the nature of the linker, and its site of attachment. Accordingly, a hydrolytic stability profile of four cocaine haptens (GNNA, GNNS, GNE, and GNC) was produced, and these results were compared through each hapten's immunological properties, which were generated via active vaccination. From this group of four, three of the haptens, GNE, GNNA, and GNC, were further examined in an animal behavioral model, and findings here were again measured in relationship to hapten stability. We demonstrate a corresponding relationship between the half-life of the hapten and its immunogenicity, wherein haptens presenting a fully representative cocaine framework elicited higher concentrations of cocaine-specific IgG in sera and also conferred better protection against cocaine-induced locomotor activity. Our results indicate that hapten half-life plays an important role in vaccine immunogenicity and this in turn can impact animal behavioral effects when challenged with a drug of abuse.

subject areas

  • Animals
  • Cocaine
  • Drug Stability
  • Haptens
  • Mice
  • Molecular Structure
  • Vaccines
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Research

keywords

  • anticocaine vaccine
  • hapten
  • immunogenicity
  • kinetics
  • psychomotor stimulant effects
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Identity

PubMed Central ID

  • PMC3946501

International Standard Serial Number (ISSN)

  • 1543-8384

Digital Object Identifier (DOI)

  • 10.1021/mp400214w

PubMed ID

  • 23927436
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Additional Document Info

start page

  • 4176

end page

  • 4184

volume

  • 10

issue

  • 11

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