ERI: evaluation of the immune response to lyme disease antigens using bacterially-derived outer membrane vesicles

This $199,984 Project Grant awarded by the National Science Foundation (NSF) Engineering program (CFDA 47.041) aims to increase the fundamental understanding of the immune response to various Lyme disease antigens using bacterial outer membrane vesicles (OMVs) as a novel carrier system. The research objectives are to: 1) explore fusion proteins as a proof of concept to present full Borrelia burgdorferi (BB) antigens on OMVs, 2) determine the potential to express multiple BB antigen epitopes on the OMV surface simultaneously, and 3) evaluate the effect of these single and multi-antigenic OMV particles on the adaptive immune response in animal models. This research is expected to inform more effective strategies for modulating the host immune response to BB infection and shape a new paradigm around Lyme disease immunology and vaccination techniques. The award was granted to the Trustees of Union College in Schenectady, New York and is scheduled to run from June 1, 2024 to May 31, 2026.

Abstract

Lyme disease is the most common vector borne disease (human illness caused by parasites, viruses, or bacteria) in the united states. IT is caused by bacteria that are spread through the bite of ticks. Research shows that the immune response to lyme disease is highly variable and depends on many factors. Lyme antigens have been shown to produce a protective immune response in certain situations. In other situations or forms, these same antigens have been shown to produce a large immune response but no protection. Due to this lack of consistency, this project aims to study the impact of specific lyme disease antigens on the immune response using a novel carrier system. The immune system response will be tested using outer membrane vesicles (OMVS). OMVS are ultra-small pieces of bacteria that will be used to carry multiple lyme proteins. The immune response generated by these OMVS will first be measured. Then, IT will be compared to the response generated by OMVS carrying only one lyme protein. This research will help identify which proteins are required to create a strong and protective immune response. In the long-term, this will lead to improved vaccination strategies against lyme disease. Undergraduate students will have the opportunity to develop biomedical engineering research skills through participation in this project. Additional students will be introduced to this research through its inclusion in a new course. Lastly, lyme disease is a prevalent problem that impacts new york residents. Results from this work will be of great interest to the general public. In response to this interest, undergraduate students will prepare and lead a publicly accessible presentation and discussion of this research. This will increase the public?S science literacy and help students gain skills communicating science to a general audience. Lyme disease is an infectious disease caused by the bacteria borrelia burgdorferi (BB), spread to humans by the black-legged tick. Research indicates that there is wide variation in the immune response to BB antigens due to a variety of factors, often resulting in incomplete protection. Outer membrane vesicles (OMVS), spherical lipid bilayers naturally derived from bacteria, have been shown to induce a strong and protective immune response in animal models, even when used in combination with poorly immunogenic antigens. This project aims to increase fundamental understanding of the immune response to various lyme antigens using the OMV background and determine if the immune response to a physical mixture of single-antigen OMVS is equal to the immune response of multivalent OMVS. These objectives will be accomplished by: 1) exploring fusion proteins as a proof of concept to present full BB antigens on OMVS; 2) determining the potential to express multiple BB antigen epitopes on the OMV surface simultaneously; and 3) evaluating the effect of these single and multi-antigenic particles on the adaptive immune response of two animal models. These studies will help inform more effective tailoring strategies for modulating the host immune response to BB infection, potentially shaping a new paradigm around the study of lyme disease immunology and effective vaccination techniques required to prevent BB infection. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the foundation's intellectual merit and broader impacts review criteria.- subawards are not planned for this award.