Mixed for the Perfect Match

Courtesy Photo | A nanolipoprotein-based subunit vaccine is produced by mixing scaffold proteins and lipids with a surfactant that increases its spreading and wetting properties. The proteins and lipids self-assemble into a disk-like structure when the surfactant is removed through dialysis. (LLNL image)  

FT. BELVOIR, VA, UNITED STATES

02.06.2023

Courtesy Story

Defense Threat Reduction Agency's Chemical and Biological Technologies Department

Harmful biological pathogens, such as viruses, bacteria, fungi, protozoa, and worms, continue to pose a threat to the Joint Force. To combat these natural challenges and better defend warfighters from bioterrorism and biowarfare, the Defense Threat Reduction Agency’s (DTRA) Chemical and Biological Technologies Department in its role as the Joint Science and Technology Office (JSTO) for the Chemical and Biological Defense Program collaborated with researchers at Lawrence Livermore National Laboratory (LLNL) to create and evaluate a nanolipoprotein (NLP)-based multipathogen vaccine platform that can be used as a single vaccine against a range of biological pathogens.

Vaccination is perhaps the most effective public health intervention to fight against harmful biological pathogens, and there have been several accomplishments in vaccine development to win the war against deadly bugs. However, DTRA JSTO anticipates emerging threats the Joint Force may face in the future, and it knows there is a continuous confrontation of longstanding, emerging, and possible known and unknown biological threats in the current biothreat platform.

Particularly beneficial to the Joint Force is that researchers have shown NLP subunit vaccines can be freeze-dried, stored for months at room temperature, and rehydrated without losing their potency, making them easy to transport to deployed units in the field. “Subunit” vaccines, also called “acellular” vaccines, do not use the whole pathogen to enhance the protective immune response, but rather the purified part of the pathogens, such as a protein or polysaccharide (several sugar molecules bonded together), that can stimulate immune cells and generate a protective immune response.

The concept of NLP particles research at LLNL is a breakthrough in vaccine development to protect warfighters and first responders against bioterrorism. The goal is to use the NLP platform to create a vaccine incorporating antigens from multiple pathogens and protect the Joint Force from several high-priority threats, including Francisella tularensis (which causes tularemia also known as rabbit fever), Yersinia pestis (which causes plague), and Burkholderia pseudomallei (which causes melioidosis also known as Whitmore's disease). LLNL with support from DTRA JSTO and researchers at the University of New Mexico Health Sciences Center previously showed the success of this approach against tularemia, which can be deadly if not treated, and this effective NLP-based subunit vaccine will serve as a foundation for enhancing capability and incorporating multiple-antigen targets to develop multipathogen vaccines.

NLPs are water-soluble, biocompatible, nanoscale platforms with favorable features of natural occurrence and structural mimics of cell membranes to connect to other molecules. NLPs are produced by mixing scaffold proteins and lipids with a surfactant that increases its spreading and wetting properties. The proteins and lipids self-assemble into a disk-like structure when the surfactant is removed through dialysis. NLPs allow the targeted delivery of antigens directly to antigen-presenting cells, which then present those antigens to T cells and boost the immune system against the foreign microorganism. This technology can also be used for cancer immunotherapy, which deploys the body’s own immune system to fight cancer.

In addition to the use of NLPs against F. tularensis and influenza, DTRA and LLNL researchers continue to explore the potential of this platform to customize targeted vaccines for multiple types of pathogens quickly. An LLNL team with researchers at the University of New Mexico found that using a combination of multiple antigen types was critical when single antigens alone provided only partial protection.

The NLP platform can work broadly by providing the foundation to fabricate effective vaccines targeted at multiple biothreats. Since the particles are naturally present in the human body, vaccines produced using the NLP platform are less likely to result in toxicity and will avoid issues associated with current vaccines that involve injecting a live attenuated organism.

The resulting NLP provides a platform for attaching other molecules to produce a potent, safe, and targeted vaccine. Vaccine candidates can be easily incorporated inside lipid complexes, which can be optimized to improve binding, avoid degradation, and improve the release of the therapeutic payload, which will better protect the Joint Force, the nation, and our allies.

POC: Julie Barbaras, Ph.D., [e-mail]

• Date Taken: 02.06.2023
• Date Posted: 02.06.2023 16:00
• Story ID: 437955
• Location: FT. BELVOIR, VA, US