The issue that the engineers are wrestling with is that when vaccines are delivered to the lungs, the lungs often clear away the vaccine before an immune response is provoked.
Darrell Irvine, an MIT (Massachusetts Institute of Technology) professor of materials science, engineering and biological engineering, lead the team of researchers to develop the nanoparticles, which may end up resulting in better flu and other infectious disease vaccines, as well as those that prevent sexually transmitted diseases such as HIV, herpes and HPV (human papilloma virus).
Irvine and colleagues describe the nanoparticle vaccine in the cover story for the Sept. 25 issue of Science Translational Medicine.
"We hope the enhanced stability of these lipid capsules, which leads to much better vaccine uptake in the airways, will overcome one significant limitation of many mucosal vaccine formulations," Irvine told BioPharma-Reporter.com.
The nanoparticle technology has been patented and licensed by Vedantra, which is now developing infectious-disease and cancer vaccines. The research was funded by the National Cancer Institute, the Ragon Institute, the Bill and Melinda Gates Foundation, the US Department of Defense and the US National Institutes of Health.
Irvine added that Vedantra "is developing the scaleup manufacturing of these particles" and that the company "hopes to take lipid nanocapsules vaccines into clinical trials in the next 18 months to 2 years."
How it Works
The Science article notes that “eliciting cellular immune responses at mucosal portals of entry is of great interest for vaccine development against mucosal pathogens.
“We describe a pulmonary vaccination strategy combining Toll-like receptor (TLR) agonists with antigen-carrying lipid nanocapsules [interbilayer-crosslinked multilamellar vesicles (ICMVs)], which elicit high-frequency, long-lived, antigen-specific effector memory T cell responses at multiple mucosal sites,” Irvine writes.
The proteins that make up the vaccine are basically encased in a sphere made of several connected lipid layers that make the particles more durable.
The nanocapsules, which took two years to develop, also “primed 13-fold more T cells than did equivalent soluble vaccines, elicited increased expression of mucosal homing integrin α4β7+, and generated long-lived T cells in both the lungs and distal (for example, vaginal) mucosa strongly biased toward an effector memory (TEM) phenotype,” according to the article.
The activation of T cells is necessary for the immune system to remember the vaccine particles so that it will be primed to respond again during an infection.
"It's like going from a soap bubble to a rubber tire. You have something that's chemically much more resistant to disassembly," Irvine said in a statement.
And although only a handful of mucosal vaccines have been approved for human use, they are becoming increasingly common recently with nasal-delivered flu vaccines, and other mucosal vaccines against cholera, rotavirus and typhoid fever.
The particles also hold promise for delivering cancer vaccines. The MIT researchers implanted mice with melanoma tumors that were engineered to express ovalbumin, a protein found in egg whites. Three days later, they vaccinated the mice with ovalbumin and found that mice given the nanoparticle form of the vaccine completely rejected the tumors, while mice given the uncoated vaccine did not.
Irvine noted that in the case of cancer vaccines, further studies need to be conducted with more challenging tumor models.