Part 2: Antigen Selection Pipeline

2.1. Overview

In this section, we’ll develop a pipeline to identify antigen candidates for an mRNA vaccine against Acinetobacter baumannii, a Gram-negative bacterium that thrives in a variety of environmental conditions. It is commonly found in hospital environments and causes infections such as meningitis, wound infections, and pneumonia. A. baumannii can spread through respiratory-care gear, wound-care instruments, humidifiers, surgical instruments, door knobs, and even mop heads. The bacteria usually target immunocompromised individuals, elevating morbidity and mortality rates by 26.5-91%. Broad-spectrum antibiotics are the most common form of treatment. Yet, the threat posed by the bacteria has grown significantly over the past 15 years, as they have shown increasing resistance to most antibiotics. Currently, there are no vaccines against A. baumannii in phase I-III/clinical trials, which has been designated as a critical pathogen by WHO.

How was this pipeline developed?

This pipeline was initially developed to suggest candidates against Klebsiella pneumoniae, a bacterium ranked as the 4th highest cause of infection-related deaths across all age groups. In 2019, it is estimated that the bacteria directly caused over 642,000 deaths globally, including over 124,000 neonatal deaths, all associated with AMR. Long-term, if _K. pneumoniae continues to develop resistance to last-resort antibiotics without new ones being discovered, medical procedures such as surgeries may become riskier or even infeasible due to the possibility of contracting an untreatable infection.

The original pipeline was initially a replication of Mehmood et al.. It was then upgraded to use the latest bioinformatics tools to further improve antigen suggestions for K. pneumoniae. After the upgraded pipeline was run against A. baumannii, a less analyzed organism, one of the tools was switched to improve the consistency of prediction vs. experimentally determined localization - if interested in more information, look out for a note in step 4.

With that said, it’s time to start the most hands-on section of this guide. To make it easier to understand, we’ll do it along the way, with a final subsection dedicated to the overall picture.