Agglutination of Borreliella burgdorferi by Transmission-Blocking OspA Monoclonal Antibodies and Monovalent Fab Fragments

Lyme disease vaccines based on recombinant uter urface rotein A (OspA) elicit protective antibodies that interfere with tick-to-host transmission of the disease-causing spirochete Borreliella burgdorferi. Another hallmark of OspA antisera and certain OspA monoclonal antibodies (MAbs) is their capaci...

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Veröffentlicht in:Infection and immunity 2022-09, Vol.90 (9), p.e0030622-e0030622
Hauptverfasser: Frye, Amber M, Ejemel, Monir, Cavacini, Lisa, Wang, Yang, Rudolph, Michael J, Song, Renjie, Mantis, Nicholas J
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Sprache:eng
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Zusammenfassung:Lyme disease vaccines based on recombinant uter urface rotein A (OspA) elicit protective antibodies that interfere with tick-to-host transmission of the disease-causing spirochete Borreliella burgdorferi. Another hallmark of OspA antisera and certain OspA monoclonal antibodies (MAbs) is their capacity to induce B. burgdorferi agglutination , a phenomenon first reported more than 30 years ago but never studied in molecular detail. In this report, we demonstrate that transmission-blocking OspA MAbs, individually and in combination, promote dose-dependent and epitope-specific agglutination of B. burgdorferi. Agglutination occurred within minutes and persisted for hours. Spirochetes in the core of the aggregates exhibited evidence of outer membrane (OM) stress, revealed by propidium iodide uptake. The most potent agglutinator was the mouse MAb LA-2, which targets the OspA C terminus (β-strands 18 to 20). Human MAb 319-44, which also targets the OspA C terminus (β-strand 20), and 857-2, which targets the OspA central β-sheet (strands 8 to 10), were less potent agglutinators, while MAb 221-7, which targets β-strands 10 to 11, had little to no measurable agglutinating activity, even though its affinity for OspA exceeded that of LA-2. Remarkably, monovalent Fab fragments derived from LA-2, and to a lesser degree 319-44, retained the capacity to induce B. burgdorferi aggregation and OM stress, a particularly intriguing observation considering that "LA-2-like" Fabs have been shown to experimentally entrap B. burgdorferi within infected ticks and prevent transmission during feeding to a mammalian host. It is therefore tempting to speculate that B. burgdorferi aggregation triggered by OspA-specific antibodies may in fact reflect an important biological activity .
ISSN:0019-9567
1098-5522
DOI:10.1128/iai.00306-22