Immunodominant Extracellular Loops of FadL Outer Membrane Proteins Elicit Antibodies with Opsonic and Growth-inhibitory Activities

Overview

Journal bioRxiv

Date 2024 Aug 12

PMID 39131275

Authors

Kristina N Delgado

Melissa J Caimano

Isabel C Orbe

Crystal F Vicente

Carson J La Vake

Andre A Grassmann

M Anthony Moody

Justin D Radolf

Kelly L Hawley

Affiliations

Soon will be listed here.

Abstract

The global resurgence of syphilis has created a potent stimulus for vaccine development. To identify potentially protective antibodies (Abs) against (), we used thioredoxin (Trx) to display extracellular loops (ECLs) from three outer membrane protein families (outer membrane factors for efflux pumps, eight-stranded β-barrels, and FadLs) to assess their reactivity with immune rabbit serum (IRS). Five ECLs from the FadL orthologs TP0856, TP0858 and TP0865 were immunodominant. Rabbits and mice immunized with these five Trx constructs produced ECL-specific Abs that promoted opsonophagocytosis of by rabbit peritoneal and murine bone marrow-derived macrophages at levels comparable to IRS and mouse syphilitic serum. ECL-specific rabbit and mouse Abs also impaired viability, motility, and cellular attachment of spirochetes during cultivation. The results support the use of ECL-based vaccines and suggest that ECL-specific Abs promote spirochete clearance via Fc receptor-independent as well as Fc receptor-dependent mechanisms.

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