Aldehyde modification and alum coadjuvancy enhance anti-TNF-α autovaccination and mitigate arthritis in rat

Alfonso Bavoso, Angela Ostuni, Jolanda De Vendel, Angelo Bracalello, Tatiana Shcheglova, Sudesh P Makker, Alfonso Tramontano

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Experimental vaccination to induce antibodies (Abs) capable of cytokine antagonism shows promise as a novel immunotherapy for chronic inflammatory disease. We prepared a hybrid antigen consisting of residues 141-235 of rat TNF-α fused to the C-terminus of glutathione-S-transferase (GST), chemically modified to incorporate aldehyde residues, for development of an auto-vaccine eliciting anti-rTNF-α Abs. In rat immunization the soluble aldehyde-modified fusion protein did not generate observable Ab responses. By contrast, vaccination with the aldehyde-modified fusion protein adsorbed on alum induced anti-TNF-α autoAbs with high titer and neutralizing activity. Induction of adjuvant arthritis in rats pre-immunized with unmodified fusion protein or a control protein in alum resulted in severe inflammation and joint damage, whereas the disease induced in rats immunized with the aldehyde-bearing fusion protein in alum was markedly attenuated. Similar results were obtained in a collagen-induced rat arthritis model. Anti-collagen II IgG Ab titers did not deviate significantly in groups pre-immunized with modified fusion protein and control protein, suggesting that anti-TNF vaccination did not skew the immune response related to disease induction. This study demonstrates synergy between particulate alum and protein bound carbonyl residues for enhancement of protein immunogenicity. The antigen-specific co-adjuvant system could prove advantageous for breaking tolerance in emerging auto-vaccination therapies targeting inflammatory cytokines as well as for enhancing a broader category of subunit vaccines. Aldehyde adduction introduces a minimal modification which, together with the established use of alum as a safe adjuvant for human use, could be favorable for further vaccine development.

Original languageEnglish (US)
Pages (from-to)400-407
Number of pages8
JournalJournal of Peptide Science
Volume21
Issue number5
DOIs
StatePublished - May 1 2015

Keywords

  • adjuvant
  • aldehyde adduction
  • alum
  • auto-vaccination
  • autoantibody
  • rheumatoid arthritis
  • tumor necrosis factor-α

ASJC Scopus subject areas

  • Organic Chemistry
  • Drug Discovery
  • Pharmacology
  • Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Structural Biology

Fingerprint Dive into the research topics of 'Aldehyde modification and alum coadjuvancy enhance anti-TNF-α autovaccination and mitigate arthritis in rat'. Together they form a unique fingerprint.

  • Cite this