Conjugation of a self-antigen to papillomavirus-like particles allows for efficient induction of protective autoantibodies
Bryce Chackerian, … , Douglas R. Lowy, John T. Schiller
Bryce Chackerian, … , Douglas R. Lowy, John T. Schiller
Published August 1, 2001
Citation Information: J Clin Invest. 2001;108(3):415-423. https://doi.org/10.1172/JCI11849.
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Article

Conjugation of a self-antigen to papillomavirus-like particles allows for efficient induction of protective autoantibodies

Abstract

High avidity and long-lasting autoantibodies to a self-polypeptide (TNF-α) were generated after parenteral vaccination of mice with low doses of virus-like particle–based (VLP-based) vaccines that were constructed by linking mouse TNF-α peptides to the surface of papillomavirus VLPs. High-titer autoantibodies were induced with or without coadministration of potent conventional adjuvants, but were enhanced by coadministration of CFA. Compared with immunization with the fusion protein alone, attachment to VLPs increased autoantibody titers 1,000-fold. A comparison of Ab responses against the self (TNF-α) and foreign components of the fusion protein showed that VLP conjugation abrogated the ability of the humoral immune system to distinguish between self and foreign. Similar levels of IgM were detected to self and foreign epitopes regardless of the assembly state of the antigen, suggesting that conjugation of self-peptides to VLPs promotes survival or expansion of mature autoreactive B cells. In a mouse model, vaccination with conjugated particles inhibited development of type II collagen-induced arthritis. Together, these results suggest a potentially flexible method to efficiently generate autoantibodies against specific self-proteins that mediate arthritis and other diseases.

Authors

Bryce Chackerian, Douglas R. Lowy, John T. Schiller

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Figure 1

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Binding of SA–TNF-α fusion protein to biotinylated VLPs. (a) Drawing sum...
Binding of SA–TNF-α fusion protein to biotinylated VLPs. (a) Drawing summarizing conjugated vaccine construction. BPV L1 VLPs were coated with activated biotin and then purified on a linear sucrose gradient. Biotinylated particles were incubated with purified SA–TNF-α fusion protein to generate conjugated particles. (b) Binding of SA–TNF-α fusion protein to VLPs. Binding of recombinant SA or purified SA–TNF-α(3–22) to wild-type or biotinylated VLPs was measured by ELISA. (c) Cosedimentation of biotinylated VLPs with SA–TNF-α(3–22). Biotinylated VLPs were incubated with SA–TNF-α(3–22) and then separated on a 24–54% sucrose gradient. Gradient fractions were analyzed by Western blot analysis, using an anti-L1 mAb (mAB837) (top panel) or an anti-SA Ab (bottom panel). Fraction 1 represents the bottom and fraction 10 represents the top of the gradient.