Design of a broadly reactive Lyme disease vaccine

Heather D Kamp,Pradeep K Dhal,Ondrej Hajdusek,Ram Dharanipragada,Gary J Nabel,Bijaya Sharma,Kurt A Swanson,Aurelie Kern,Linden T Hu,Radek Sima,Ronnie R Wei,Chih-Jen Wei

doi:10.1038/s41541-020-0183-8

Heather D Kamp, Pradeep K Dhal + Show 10 more

Open Access

https://doi.org/10.1038/s41541-020-0183-8

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Abstract

A growing global health concern, Lyme disease has become the most common tick-borne disease in the United States and Europe. Caused by the bacterial spirochete Borrelia burgdorferi sensu lato (sl), this disease can be debilitating if not treated promptly. Because diagnosis is challenging, prevention remains a priority; however, a previously licensed vaccine is no longer available to the public. Here, we designed a six component vaccine that elicits antibody (Ab) responses against all Borrelia strains that commonly cause Lyme disease in humans. The outer surface protein A (OspA) of Borrelia was fused to a bacterial ferritin to generate self-assembling nanoparticles. OspA-ferritin nanoparticles elicited durable high titer Ab responses to the seven major serotypes in mice and non-human primates at titers higher than a previously licensed vaccine. This response was durable in rhesus macaques for more than 6 months. Vaccination with adjuvanted OspA-ferritin nanoparticles stimulated protective immunity from both B. burgdorferi and B. afzelii infection in a tick-fed murine challenge model. This multivalent Lyme vaccine offers the potential to limit the spread of Lyme disease.

Highlights

Lyme borreliosis is a zoonotic disease caused by Borrelia burgdorferi sl and is transmitted to humans and canines by the bite of an infected tick
outer surface protein A (OspA) serotype 1 from B. burgdorferi strain B31 was fused to ferritin and expressed in E. coli
Nanoparticles of the expected size were isolated as measured by size exclusion chromatography (SEC) and dynamic light scattering (DLS)

Summary

Introduction

Lyme borreliosis is a zoonotic disease caused by Borrelia burgdorferi sl and is transmitted to humans and canines by the bite of an infected tick. Lyme disease affects more than 300,000 people in the U.S yearly, causing recurrent fatigue, cardiac arrhythmias, arthralgias, and neurological abnormalities[1,2], costing the U.S health care system more than $1.3 billion dollars a year[3]. In Europe, Lyme disease has spread to new regions geographically and its incidence has increased, estimated at 230,000 cases per year[4,5,6,7]. The bacteria can spread from the skin to the heart, joints, and nervous system in individuals not treated with antibiotics early in infection. Vaccination represents a key public health intervention that would prevent Lyme disease by preventing primary infection. A vaccine needs to protect both children and adults

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