Disrupted adenovirus-based vaccines against small addictive molecules circumvent anti-adenovirus immunity

Bishnu P. De, Odelya E. Pagovich, Martin J. Hicks, Jonathan B. Rosenberg, Amira Y. Moreno, Kim D. Janda, George F. Koob, Stefan Worgall, Stephen M. Kaminsky, Dolan Sondhi, Ronald Crystal

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15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)58-66
Number of pages9
JournalHuman Gene Therapy
Volume24
Issue number1
DOIs
Publication statusPublished - 1 Jan 2013
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

De, B. P., Pagovich, O. E., Hicks, M. J., Rosenberg, J. B., Moreno, A. Y., Janda, K. D., Koob, G. F., Worgall, S., Kaminsky, S. M., Sondhi, D., & Crystal, R. (2013). Disrupted adenovirus-based vaccines against small addictive molecules circumvent anti-adenovirus immunity. Human Gene Therapy, 24(1), 58-66. https://doi.org/10.1089/hum.2012.163