Serological correlates of disseminated Borrelia burgdorferi infection in mouse models of tick challenge.

UNLABELLED: The mouse model of tick-mediated Borrelia burgdorferi sensu lato (Bbsl) challenge is integral to the preclinical evaluation of Lyme disease vaccines. The standard measure of vaccine efficacy is the recovery of viable spirochetes from different mouse tissues, monitored weekly for a month post challenge. Serological tests (ELISA and Western blots) with B. burgdorferi lysates, recombinant proteins, or peptides are often used as alternative or confirmatory readouts. While there are several reports suggesting that culture positivity and serology are strongly correlated, a systematic study addressing this issue is lacking. In this report, we took advantage of available data sets from large cohorts of naive and OspA actively and passively immunized mice that had been challenged with Ixodes scapularis nymphs carrying Bbsl strain B31, euthanized 3 weeks later, then assessed for culture positivity across different tissue types (ear, skin, ankle, bladder, and heart) and seropositivity using an OspC and DbpB 2-plex microsphere immunoassay (MIA) and a vmp-like sequence C6 monoplex MIA. Our results demonstrate a 96.5%-97% agreement between culture positivity and seroconversion using the OspC/DbpB and C6 MIAs, suggesting that serology provides a near-perfect readout of disseminated spirochetal infection. While some instances of culture and serological discordance could be attributed to technical errors, others likely reflect aspects of infectivity/immunological dynamics, including the possibility of abortive (non-sterilizing) B. burgdorferi infections. We conclude that serological testing provides a highly accurate and practical measure of disseminated B. burgdorferi infection in mouse models, crucial for the efficient preclinical assessment of Lyme disease vaccines. IMPORTANCE: The laboratory mouse (Mus musculus) plays an indispensable role in the testing of candidate vaccines for Lyme disease, an emerging tick-borne infection caused by the spirochete, Borrelia burgdorferi. While laboratory mice do not develop Lyme disease per se, B. burgdorferi proliferates in skin tissues following a tick bite, then disseminates to other organs over the course of days to weeks. In this report, we examined the concordance between two widely used methodologies to assess disseminated B. burgdorferi infection and offer recommendations to standardize testing across laboratories.