A Novel Self-Adjuvanting cc Particle-Based Tuberculosis Vaccine
Abstract
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, remains a major public health threat yet effective vaccines remain elusive. Mtb antigens ESAT-6 and Ag85B have shown promise as the basis of vaccines. However, developing effective immune responses to these antigens requires co-administration of immune boosters known as adjuvants, which complicates vaccine development. Another limitation of many current vaccines is the need for multiple immunizations to induce strong immunity. This proposal seeks to develop a unique Ebola virus-like particle-(eVLP)-based approach comprised of Ebola virus proteins and built in adjuvanting activity that has several advantages over existing vaccine candidates. First, introduction of the 2CARD signaling domains from the pattern recognition receptor RIG-I confers self-adjuvanting activity to the eVLPs, resulting in vigorous immune responses as compared to standard eVLPs. Second is inclusion into the platform of proven Mtb antigens that can elicit beneficial immunity. We have successfully produced highly purified eVLPs that incorporate ESAT6 and Ag85B, as well as the 2CARD domain, in various configurations. We have previously shown that "infection" of cells with VLPs containing the constructs causes robust activation of innate immune responses. We now build on these findings by demonstrating rapid induction of antibody responses to the GP surface antigen of the eVLPs following immunization of C57BL/6 mice; this puts us in good position to progress to assessment of T cell responses to the Mtb antigens in the coming year.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2022
- Accession Number
- AD1179798
Entities
People
- Joann Tufariello
Organizations
- Georgia State University