The design and development of novel vaccine candidates is an arduous undertaking, but supremely essential if we hope to combat some of the most debilitating diseases that consistently infect hosts of individuals. While there are a number of approaches to developing effective vaccines, the use of virus-like particles (VLPs) has been a popular method in the drug discovery process in the past several years.
Now, a team of researchers at the University of Oxford has a devised a technique using VLPs to speed up the development process. VLPs resemble viruses, but importantly don't harbor pathogenic genetic material and thus cannot cause disease. These particles are cleverly engineered to display one part of a pathogen to the immune system, which can elicit strong protection upon any subsequent exposure to that pathogen.
“Current techniques to develop VLP-based vaccines take time and do not always work,” explained lead author Karl Brune, a doctoral candidate in the department of biochemistry at the University of Oxford. “Whilst getting the pathogen parts to stick to the carrier VLP, often problems such as misassembly or misfolding arise that make the vaccine ineffective at generating protective immunity.”
Consequently, this failure rate often translates into high development costs when trying to generate vaccines against major diseases like malaria, HIV, and cancer.
“A more reliable way of assembling candidate vaccines could make them much cheaper and improve the chances of vaccines against these illnesses,” noted co-author Darren Leneghan, Ph.D., a postdoctoral scientist at Oxford's Jenner Institute, which specializes in vaccine development. “A faster way of assembling vaccines may also help with the rapid development of new vaccines against unforeseen disease outbreaks.”
The Oxford researchers were able to overcome some key obstacles in vaccine assembly using a laboratory-engineered protein “superglue.” The adhesive compound is made up of two component proteins—a larger protein called SpyCatcher, and a smaller protein part named SpyTag—both engineered from the bacterium Streptococcus pyogenes. When SpyTag and SpyCatcher meet, they form an unbreakable isopeptide bond. The investigators were successful in genetically engineering SpyCatcher on VLPs, which now enables scientists to easily and relatively quickly glue proteins with the small SpyTag to the SpyCatcher-VLPs.
“We tested the SpyCatcher-VLP/SpyTag-antigen combination using a range of malarial and cancer-relevant antigens,” remarked Brune. “This showed that linking can be done simply and quickly to produce stable vaccines that generated robust antibody responses.”
The findings from this study were published recently in Scientific Reports through an article entitled “Plug-and-Display: decoration of Virus-Like Particles via isopeptide bonds for modular immunization.”
The researchers were excited by their findings and felt that the technique should speed up the development of new vaccines, as well as aid in other medical applications of nanoparticles. However, they tempered their enthusiasm by stating that more work needs to be performed to tweak the efficiency of the new method.
“We need to do more research, both to see if we can use Tag/Catcher fusion with other diseases and to test effectiveness in live rather than lab conditions, ” Brune concluded.