In research published in Nature biomedical engineering a team of scientists at Northwestern University’s International Institute for Nanotechnology (IIN) explored the effects of structural changes to cancer vaccines. Using chemistry and nanotechnology they changed the location of adjuvants and antigens on and within a nanoscale vaccine with positive consequences.
The team used spherical nucleic acid (SNA) nanoparticles to “investigate how the spatial distribution and placement of two antigen classes affect antigen processing, cytokine production, and the induction of memory”. Their conclusion is that “the structural design of multi-antigen vaccines substantially impacts their efficacy”.
Current vaccine approaches
News Medical describes the “conventional” vaccine approach as a blend of antigen and adjuvant, which is then injected into the patient. As there is “no control over the vaccine structure” there is “limited control over the trafficking and processing of the vaccine components”. Thus, we can’t control the efficacy of the vaccine.
Dr Michelle Teplensky, one of the study authors, suggests that a “challenge” associated with this “blended mish mosh” approach is that “an immune cell might pick up 50 antigens and 1 adjuvant or 1 antigen and 50 adjuvants”. However, there “must be an optimum ratio of each that would maximise the vaccine’s effectiveness”.
The study indicates that “increasing efforts have been made to develop vaccines targeting identified tumour-associated proteins”. However, although there are “some benefits” to these, “many are designed to primarily activate cytotoxic T cells”.
“Tumour can have considerable heterogeneity and high mutational burdens that allow for easy escape of immune surveillance.”
With cytotoxic T cell activity reliance, current vaccines are “inadequate” and necessitate “vaccines containing antigens targeting multiple immune cell types to induce enhance tumour remission”. Dr Teplensky emphasises that the “more types of cells the immune system has to go after tumours, the better”.
What are they changing?
SNAs, a structural platform developed by Professor Chad Mirkin, Director of the IIN, enable scientists to identify the specific quantities of antigens and adjuvants being delivered to cells, as well as how they are being presented and processed. This novel approach, “rational vaccinology” as Professor Mirkin calls it, recognises that the structural presentation of a vaccine is just as important as its contents.
Professor Mirkin suggests that rational vaccinology allows vaccines to “deliver the precise dose of antigen and adjuvant to every immune cell” so that they are “all equally primed to attack cancer cells”.
“If your immune cells are soldiers, a traditional vaccine leaves some unarmed; our vaccine arms them all with a powerful weapon with which to kill cancer.”
In the study, the authors explore the “vaccine-design space involving multiple cell-targeting antigens.” The vaccines they investigated respond to specific structural placements of antigen targets to “prime the immune system most effectively”. The most potent approach for a cancer vaccine structure in this work involved attaching two different antigens to an SNA comprising a shell of adjuvant. This resulted in a 30% increase in antigen-specific T cell activation. In several animal models the nanostructures stalled tumour growth.
What will this mean for the future?
The authors state that the power to “optimise antigen presentation” to meet the “desired signalling profile” will be “critical” to the future of powerful vaccines. They hope that the developments in their study will offer a “path forward to rethink the design of vaccines for cancer and other diseases”.
With “remarkable” data, they produced a potent vaccine with the same compositional features as a less effective vaccine. However, their success may not be limited to cancer. Another possible advantage to rational vaccinology is the ability to change the vaccine to apply to a different disease. Dr Teplensky hopes that their work affords potential for “almost any type of cancer” and “vaccines across the board”.