Rapid Detection of Candidates for Vaccines Against Biothreat Agents

Magdalena Franco | 18-LW-039

Project Overview

Peptide-based subunit vaccines are coming to the forefront of current vaccine approaches, with safety and cost-effective production among their top advantages. Peptide vaccine formulations consist of multiple, synthetic, linear epitopes that trigger desired immune responses, and in combination can result in robust immune memory. The advantage of peptide epitopes are their simple structure, ease of synthesis, and ability to induce the immune system without complex three-dimensional conformation requirements.

Currently the identification of linear epitopes is a slow process that requires thorough characterization of previously identified protein antigen or the use of laborious techniques that require genetic manipulation of organisms. In this study we sought to develop a widely applicable screening method that enables efficient identification of B cell epitopes in proteomes of pathogenic bacteria. As a test case, we applied this method to characterize the immunoproteomes of Francisella tularensis and Burkholderia pseudomallei, bacterial agents that pose a high risk for misuse as bioweapons, and therefore are considered Tier 1 Select Agents by the Centers for Disease Control and Prevention.

The results from this study indicate enrichment of peptide mapping to known antigens, validating the efficacy of this approach. This workflow is easily adaptable to detecting peptide targets relevant to the immune system of humans and other animals. Accelerating the discovery of B cell epitopes in the proteomes of pathogens will help fuel the development of next-generation peptide vaccines and other peptide-based therapeutics to counter emerging biological threats.

Mission Impact

This effort supports Lawrence Livermore National Laboratory's mission in developing experimental approaches for timely development of life-saving countermeasures against emerging biological threats. We built on the Laboratory's core competencies in bioscience and bioengineering, specifically in the area of vaccine target identification. Peptide-based vaccines have a potential for providing faster solutions to emerging biothreats and improve our preparedness for future pandemics, thereby increasing national security.

Publications, Presentations, and Patents

Franco, M., et al. 2020. "Rapid Discovery of B-cell Epitopes for Peptide Vaccines against Biothreat Agents and Emerging Pathogens." ASM Biothreats Meeting, Arlington, VA, January 2020. LLNL-POST-802018