Researchers at Northwestern University’s International Institute for Nanotechnology (IIN) have discovered a novel method to substantially boost the effectiveness of practically any vaccine.

Researchers significantly improved the effectiveness of a nanoscale vaccination by altering the structural placement of adjuvants and antigens on and inside the vaccine via the application of chemistry and nanotechnology.

The adjuvant is a stimulant that boosts the antigen’s efficacy as the antigen targets the immune system.

The findings of the research were published in Nature Biomedical Engineering.

Lead researcher Chad A. Mirkin, director of the IIN, noted, the findings reveal that vaccine structure and not only the components is a significant aspect in determining vaccination effectiveness. The location and arrangement of the antigens and adjuvants within a single design significantly alters how the immune system perceives and reacts to them.

According to Mirkin, conventional cancer vaccines have not been very successful, but this new focus on the structure may help change that.

In order to identify the best architecture for treating each disease, Mirkin’s team has examined the impact of vaccine structure in the context of seven different cancer types, including triple-negative breast cancer, papillomavirus-induced cervical cancer, melanoma, colon cancer, and prostate cancer.

The antigen and the adjuvant are combined in the majority of conventional vaccines before being administered into a patient. There is little control over the vaccine’s composition, and as a result, there is little control over how the vaccine’s components are transported and processed. Therefore, the effectiveness of the vaccine is uncontrollable.

The problem with conventional vaccines, according to study author Michelle Teplensky, “is that out of that blended mish mosh, an immune cell might pick up 50 antigens and one adjuvant or one antigen and 50 adjuvants.

“But there must be an optimum ratio of each that would maximize the vaccine’s effectiveness.”

This new kind of modular vaccine makes use of SNAs (spherical nucleic acids), a structural platform designed and developed by Mirkin. Scientists can precisely determine how many antigens and adjuvants are being delivered to cells thanks to SNAs. The presentation and processing rates of these vaccine components may also be customized by scientists using SNAs. Such structural factors, which have a significant influence on vaccination efficacy, are generally disregarded in traditional techniques.

Mirkin developed this method for systematically controlling antigen and adjuvant sites inside modular vaccination structures, and he coined the term rational vaccinology to characterize it. The theory behind it is that the structural presentation of vaccination components is just as crucial to their effectiveness as the components themselves.

According to Mirkin, vaccines designed via rational vaccinology provide the right dosage of antigen and adjuvant to every immune cell, so they are all equally ready to target 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. 

“Which immune cell ‘soldiers’ do you want to attack your cancer cells?”

By redesigning the architecture of the vaccine to include numerous targets to aid the immune system in locating tumor cells, the team developed a cancer vaccine that quadrupled the number of T cells specific to cancer antigens and enhanced their activation by 30%.

The group looked at whether the location of two antigens inside the SNA structure (in the core vs the periphery) affected their recognition by the immune system. For an SNA that was placed in the best way, they could boost the immune response and how quickly the nanovaccine caused cytokine (a protein made by immune cells) to be made to make more T cells attack the cancer cells. The scientists also examined how the various locations influenced the immune system’s capacity to recall the invader and the durability of this memory.

The location and arrangement of the antigens and adjuvants within a single architectural design have a significant impact on how the immune system perceives and processes them, according to Mirkin.

According to the study’s findings, the most effective method for creating a cancer vaccine structure was to combine two distinct antigens with an SNA that included an adjuvant shell. Compared to a structure where the same two antigens were attached to two different SNAs, it led to 30% more antigen-specific T-cell activation and doubled the number of T cells that were dividing.

In several animal models, these modified SNA nanostructures stopped tumor development.

“It is remarkable,” Mirkin remarked. “When altering the placement of antigens in two vaccines that are nearly identical from a compositional standpoint, the treatment benefit against tumors is dramatically changed. One vaccine is potent and useful, while the other is much less effective.” 

Current cancer vaccines often work by priming cytotoxic T cells, which are only one line of protection against cancer cells. The constant mutation of tumor cells makes it simple for them to evade this immune cell monitoring, soon making the vaccination useless. If the T cell has many antigens to detect a cancer cell that is mutating, the likelihood that it will do so is increased.

Teplensky said that in order to target a tumor cell, we “need more than one type of T cell activated.”

The more cell types the immune system has at its disposal to combat cancers, the better.

To elicit more robust and long-lasting tumor remission, according to Teplensky, vaccines must include numerous antigens that target different populations of immune cells.

Another benefit of the rational vaccination method is that it is simple to change the shape of a vaccine to target a different illness, particularly when using a nanostructure like an SNA. They only replace a peptide, a portion of a cancer protein with a chemical handle that “clips” onto the structure, similar to attaching a new charm to a bracelet, according to Mirkin.

“The collective importance of this work is that it lays the foundation for developing the most effective forms of vaccine for almost any type of cancer,” Teplensky added. “It is about redefining how we develop vaccines across the board, including ones for infectious diseases.”

The significance of all of this research, according to Teplensky, is that it paves the way for the creation of the best cancer vaccines. It involves reinventing the process by which all vaccines, including those for infectious illnesses, are developed.

Mirkin, Teplensky, and colleagues earlier proved the relevance of vaccine structure for COVID-19 by developing vaccinations that produced protective immunity in 100% of mice against a deadly viral infection.

Small adjustments to the antigen positioning on a vaccination, according to Mirkin, greatly increase cell-to-cell contact, cross-talk, and cell synergy. 

“The developments made in this work provide a path forward to rethinking the design of vaccines for cancer and other diseases as a whole.” 

Image Credit: David Greedy/Getty Images


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