Disrupted adenovirus-based vaccines against small addictive molecules circumvent anti-adenovirus immunity. Academic Article uri icon

Overview

MeSH

  • Animals
  • Antibodies, Neutralizing
  • Blotting, Western
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C

MeSH Major

  • Adenoviridae
  • Caproates
  • Capsid Proteins
  • Cocaine
  • Genetic Vectors
  • Multiprotein Complexes
  • Nicotine
  • Vaccines

abstract

  • Adenovirus (Ad) vaccine vectors have been used for many applications due to the capacity of the Ad capsid proteins to evoke potent immune responses, but these vectors are often ineffective in the context of pre-existing anti-Ad immunity. Leveraging the knowledge that E1(-)E3(-) Ad gene transfer vectors are potent immunogens, we have developed a vaccine platform against small molecules by covalently coupling analogs of small molecules to the capsid proteins of disrupted Ad (dAd5). We hypothesized that the dAd5 platform would maintain immunopotency even in the context of anti-Ad neutralizing antibodies. To test this hypothesis, we coupled cocaine and nicotine analogs, GNE and AM1, to dAd5 capsid proteins to generate dAd5GNE and dAd5AM1, respectively. Mice were pre-immunized with Ad5Null, resulting in high titer anti-Ad5 neutralizing antibodies comparable to those observed in the human population. The dAd5GNE and dAd5AM1 vaccines elicited high anti-cocaine and anti-nicotine antibody titers, respectively, in both naive and Ad5-immune mice, and both functioned to prevent cocaine or nicotine from reaching the brain of anti-Ad immune mice. Thus, disrupted Ad5 evokes potent humoral immunity that is effective in the context of pre-existing neutralizing anti-Ad immunity, overcoming a major limitation for current Ad-based vaccines.

publication date

  • January 2013

has subject area

  • Adenoviridae
  • Animals
  • Antibodies, Neutralizing
  • Blotting, Western
  • Caproates
  • Capsid Proteins
  • Cocaine
  • Female
  • Genetic Vectors
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Multiprotein Complexes
  • Nicotine
  • Vaccines

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3555097

Digital Object Identifier (DOI)

  • 10.1089/hum.2012.163

PubMed ID

  • 23140508

Additional Document Info

start page

  • 58

end page

  • 66

volume

  • 24

number

  • 1