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Cross-reactive influenza antibodies from lamprey

Friday, November 08, 2013 — Poster Session IV

2:00 p.m. – 4:00 p.m.

FAES Academic Center (Upper-Level Terrace)

NIAID

IMMUNO-1

Authors

  • MO Altman
  • TR McKitrick
  • JW Stevens
  • JR Bennink
  • JW Yewdell
  • BR Herrin

Abstract

Antibodies not only protect against influenza, they also define influenza hemagglutinin (HA) antigenicity, and play an important role in understanding HA function. In addition to immunoglobulins, there exists another class of antibodies called variable lymphocyte receptors (VLRs), which recognize antigens by a different set of structural and chemical principles. Structurally similar to Toll-like receptors, VLRs use multiple leucine-rich repeats to create an antigen-binding surface. VLRs are produced exclusively by jawless vertebrates, represented today by lamprey and hagfish, where they function similar to immunolglobulin in immunity. To better understand the rules of VLR antigen recognition and probe HA structure and function in a novel manner, we immunized lamprey larvae with A/Puerto Rico/8/34 H1N1 virus (PR8). All 19 immunized animals made antibodies that reacted with PR8 by ELISA, whereas the three vehicle controls did not. A portion of these antibodies competed with known epitopes of PR8 in the HA globular head. Surprisingly, however, cross reactive antibodies that bound a H3 subtype and even very distantly related influenza B influenza were also made. Immunoblotting showed some of these cross-reactive antibodies recognized HA. We are currently exploring the basis for this intriguing cross-reactivity, which could have a number of basic and practical applications.

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