Suppression of Adaptive Immunity by Borrelia burgdorferi: An Investigation of Complex Host-Microbe Interactions

Purpose: Infection with Borrelia burgdorferi (Bb), the causative agent of Lyme Disease, induces broad suppression of the host adaptive immune response. It has been shown that short-lived germinal centers form in the lymph nodes shortly after infection, but then collapse approximately one month post-infection. The resulting adaptive immune response is characterized by unusually strong and persistent IgM production and lack of long-lived immunity. Additionally, when a group of Bb-infected mice were given a co-administered influenza vaccine, they mounted a significantly abrogated influenza-specific antibody response when compared to an uninfected group that received the same vaccine. A better understanding of how Bb manipulates host immunity can help enhance serological testing and treatment options for Lyme Disease. We aim to determine the duration of humoral immune suppression by Bb and characterize the events leading up to germinal center collapse. Methods: We will randomly assign mice to 5 groups (n=4). One group will be inoculated with a SARS-CoV-2 spike protein vaccine. The remaining 4 groups will be infected with Bb and will subsequently receive the SARS-CoV-2 vaccine at Day 0, 14, 28, or 42. We have recently tested the safety of the vaccine for use in mice. This protocol has undergone IACUC approval (IACUC-2020-0033). We will assess the SARS-CoV-2-specific antibody response at different stages of infection with Bb, which will be measured using enzyme-linked immunosorbent assays (ELISA). We will also use genetic techniques such as RT-qPCR and single-cell RNA sequencing to interrogate the events underpinning this immune suppression. Results and Conclusion: This study has not yet been completed. Although conclusions cannot yet be drawn, preliminary evidence demonstrates that the SARS-CoV-2 vaccine is safe for use in mice and induces a robust antibody response. We have recently successfully established infection in mice using Bb strain N40 and are currently examining lymph node histology of infected mice to confirm germinal center suppression in our infection model.