Innovative Metal Organic Frameworks Enhancing Vaccine Efficacy through Immune Activation

Recent breakthroughs in vaccine technology highlight how metal-organic frameworks (MOFs) can revolutionize immune response activation by combining precise antigen delivery with inherent adjuvant properties, offering promising avenues for safer, more effective vaccines.

Understanding MOFs as Vaccine Adjuvants

Numerous vaccines, including those for hepatitis B and whooping cough, are formulated using fragments of viral or bacterial proteins. These vaccines frequently incorporate additional molecules known as adjuvants, which enhance the immune system’s response to these proteins.

Traditionally, many adjuvants are composed of aluminum salts or similar substances that trigger a nonspecific immune response. However, recent research from MIT has revealed that a type of nanoparticle, referred to as a metal-organic framework (MOF), can also elicit a robust immune response. This occurs by activating the innate immune system, which serves as the body’s primary defense mechanism against pathogens, through specific cell proteins known as toll-like receptors (TLRs).

Experimental Validation with SARS-CoV-2 Proteins

In an experimental study involving mice, researchers demonstrated that this MOF could effectively encapsulate and deliver a portion of the SARS-CoV-2 spike protein, simultaneously acting as an adjuvant upon its breakdown within the cells. While further research is required to adapt these particles for vaccine applications, the findings indicate that this structural type holds promise for generating strong immune responses.

Ana Jaklenec, a principal investigator at MIT’s Koch Institute for Integrative Cancer Research and a senior author of the study, emphasizes the significance of understanding how drug delivery systems can enhance the immune response of adjuvants when designing new vaccines.

Mechanism of Action Behind ZIF-8 MOF

The focus of this research was on a MOF named ZIF-8, which consists of a framework of tetrahedral units made up of zinc ions connected to four imidazole molecules. Previous studies had established that ZIF-8 can significantly enhance immune responses, although the precise mechanism behind its activation of the immune system was not fully understood.

To investigate this mechanism, the MIT team developed an experimental vaccine comprising the SARS-CoV-2 receptor-binding protein (RBD) embedded within ZIF-8 particles. These nanoparticles measure between 100 and 200 nanometers in diameter, allowing them to access the body’s lymph nodes directly or through immune cells like macrophages.

Once inside the cells, the MOFs degrade, releasing the viral proteins. The researchers discovered that the imidazole components activate TLRs, which play a crucial role in stimulating innate immune responses.

“This process can be likened to deploying a covert operational team at the molecular level to deliver vital elements of the Covid-19 virus to the body’s immune system, where they can trigger specific immune responses and enhance vaccine effectiveness.” – Alsaiari

Immune Response Outcomes in Animal Models

RNA sequencing from lymph node cells showed that mice vaccinated with ZIF-8 particles containing the viral protein exhibited strong activation of a TLR pathway known as TLR-7, leading to increased production of cytokines and other inflammatory molecules.

Mice that received these nanoparticles produced a significantly stronger response to the viral protein than those that were vaccinated with the protein alone. “We are not only delivering the protein in a more controlled manner via nanoparticles, but the structure of these particles also acts as an adjuvant,” Jaklenec adds. “We achieved highly specific responses to the Covid protein with a dose-sparing effect compared to administering the protein alone.”

Future Prospects and Global Impact

Although this research has highlighted ZIF-8’s immunogenic capabilities, additional investigations are necessary to assess the safety and scalability of these particles for large-scale production. Even if ZIF-8 is not developed as a vaccine carrier, insights from this study could inform researchers in creating similar nanoparticles for subunit vaccine delivery.

“Typically, subunit vaccines comprise two distinct components: an antigen and an adjuvant,” Jaklenec notes. “Innovating vaccines that utilize nanoparticles with specific chemical properties can facilitate antigen delivery while activating targeted immune pathways, potentially enhancing vaccine efficacy.”

One notable advantage of developing subunit vaccines for Covid-19 is their generally lower production cost compared to mRNA vaccines. This could simplify global distribution during pandemics. Jaklenec remarks, “Subunit vaccines have been utilized for many years and tend to be less expensive to manufacture, thus increasing vaccine accessibility during crises.”

This research was supported by Ibn Khaldun Fellowships for Saudi Arabian Women and partially funded by the Koch Institute Support (core) Grant from the U.S. National Cancer Institute.