When Losing Memory is a Good Thing

FORT BELVOIR, VA, UNITED STATES

03.26.2019

Courtesy Story

Defense Threat Reduction Agency's Chemical and Biological Technologies Department

The human body is complex, highly integrated and very smart. It has evolved over time to be able to build immunities to all sorts of deadly threats. The body develops an immune memory so it can react quickly and fight future exposures to threats. Unfortunately, it also builds an immunity to medical countermeasures, vaccines and drugs used to treat those exposed to threats. The Defense Threat Reduction Agency’s Chemical and Biological Technologies Department (DTRA CB) is funding research to ensure current countermeasures remain effective options for warfighters.

The body’s immune memory presents a serious problem for warfighters who may need to receive repeated countermeasures to protect them from, and treat them for, recurring exposure to biological threats.
Currently there are many polymer-based prophylaxes and therapeutics that trigger the body’s immune response once administered. This means only the first dose will provide maximum efficiency and protection. Subsequent doses are not as effective because the body is building an immunity to the drug being administered.

Being able to develop a means of administering a drug without triggering the body’s immune system would maximize the efficiency of a drug every time it is administered.

The immunological safety of polymers has been increasingly recognized as critically important, but poorly understood. Principal Investigator Shaoyi Jiang, Ph.D., and his team at the University of Washington, in a project funded by DTRA CB, systemically explored the immunogenic risk of poly ethylene glycol (PEG) and poly carboxybetaine (PCB) polymers. The team conjugated the polymers to a series of carrier proteins with escalating immunogenicity and assessed the tendency of anti-polymer antibody (Ab) induction in C57BL/6J mice.

A quantitative correlation between the level of anti-PEG Ab responses and the immunogenicity of carrier proteins was clearly observed and established, validating the haptenic (a small molecule that reacts with a specific antibody but does not induce an immune response unless bound to a larger molecule, usually a protein) character of PEG while disclosing its strong immunogenic potential.

This correlation also allows the estimation of potential PEG-induced immune responses in biopharmaceutical applications based on the protein immunogenicity.

In stark contrast, negligible levels of anti-PCB Abs were observed in the whole study, even when PCB was conjugated to highly immunogenic KLH as confirmed by enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) tests. Such minimal immunogenicity of PCB was insensitive to the increased protein immunogenicity, suggesting the low immunogenic risk of zwitterionic PCB polymers.

Adverse immune responses by the body can prevent successfully treating exposure to a biological threat. However, Jiang and his team believe their new, alternative polymer will not evoke the body’s immunity memory response, allowing better protection for warfighters as they will be able to receive multiple, effective countermeasure treatments to threats.

POC: Alison Director-Myska, Ph.D.: [e-mail]

• Date Taken: 03.26.2019
• Date Posted: 03.26.2019 09:33
• Story ID: 315671
• Location: FORT BELVOIR, VA, US