UCLA researchers have developed injectable, cell-free, and biomaterial-based microparticles that can engage with tissue resident immune cells and enhance long-term immunity. It is the first biomaterial-based, targeted approach to induce T memory stem cells (TMSCs) in vivo. The approach was demonstrated for SARS-CoV-2 but can be used for any vaccine. This approach could also be used in the delivery of cancer vaccines. This approach addresses the unmet need of enhancing the vaccination effects in the elderly population, which suffers from compromised long-term immunity due to immunosenescence.
BACKGROUND:
Vaccines prime human immune systems to protect individuals against various serious infectious diseases, including SARS-CoV-2, which has caused millions of deaths worldwide. The high susceptibility and death rate of the elderly due to infectious diseases, such as SARS-CoV-2 and influenza, present a major challenge to our healthcare system. Conventional vaccines do not generate effective immune memory in the elderly due to immunosenescence. Aging immune systems usually fail to induce long-lived memory T cells, which decline in older years. Also, conventional vaccines do not effectively prime T memory stem cells. Thus, to protect the elderly population, it is critical to boost the generation of T memory stem cells (TMSCs) that can provide long-term immunity.
TMSCs are unique subsets of memory T cells endowed with the stem cell-like ability to self-renew with the multipotent capacity to reconstitute the entire spectrum of memory and effector T cells. Compared with other memory T cell subsets, TMSCs demonstrate a faster response to antigen stimulation, which will make the immunization more effective. In addition, TMSC preferentially survive after the elimination of antigens, and stably persist for many years. As a result, increased T cell loss after the peak period is a main reason of diminishing memory in the elderly. Although there is no targeted approach to boost up formation of TMSCs during a standard vaccination, evidence suggests that successful generation of TMSC during vaccination can significantly improve the cellular immunity in the elderly. Cumulative evidence in mice, nonhuman primates as well as humans indicate that TMSCs could be leveraged therapeutically to enhance the efficacy of vaccines for infectious diseases and cancers.
INNOVATION:
UCLA researchers have developed immunomodulatory injectable microparticles to mimic the functions of artificial antigen presenting cells (aAPCs) and to induce TMSCs against the antigen of choice (infectious disease proteins or cancer-specific markers). These particles naturally and harmlessly degrade in the body over weeks. As a proof of concept, the UCLA team utilized this targeted approach to induce T memory stem cells (TMSCs) in vivo to enhance SARS-CoV-2 vaccination. The injectable particles have tunable physicochemical properties, and will incorporate multiple functional aspects: (i) recruit tissue resident T cells, (ii) provide cell- and extracellular matrix (ECM)-mimicking environment for cellular engagement, (iii) provide optimal activation signals to activate naìˆve T cells, (iv) release cytokines and small molecules to induce the formation of TMSCs, and (v) co-deliver a vaccine candidate, i.e., a peptide pool created based on the spike protein of SARS-CoV-2. This is the first biomaterial-based, targeted approach to induce TMSCs in vivo to enhance vaccination. The proposed concept and innovative biomaterials platform are a groundbreaking approach to enhance the vaccination effects in the elderly population, addressing a critical unmet medical challenge. The proposed technology is a first-in-class platform that is cell-free, easy-to-handle, injectable, biodegradable, and scalable with modular antigen/cytokine/adjuvant loading and release properties. This invention will have wide applications in immunomodulation for many infectious diseases and cancer.
POTENTIAL APPLICATIONS:
- Enhance SARS-CoV-2 vaccination.
- Enhance influenza vaccination.
- Enhance vaccination for other infectious diseases in which long-term immunity wanes (e.g., Streptococcus pneumoniae)
- Enhance vaccine-based cancer therapies.
- Enhance disease treatments with enhanced long-term immunity.
ADVANTAGES:
- This platform is low cost compared to cell-based vaccines.
- This method can be scaled up in Good Manufacturing Practice (GMP) facilities to provide affordable vaccine booster against endemic and epidemic pathogens such as SARS-CoV-2.
- This TMSC booster co-delivered with vaccines will stimulate long-term immunity, offering protection for vulnerable populations such as the elderly and the immunocompromised.
DEVELOPMENT-TO-DATE:
The invention was initiated in April 2020. The invention was published in ACS Nano, a premier journal in bioengineering, on Feb 21, 2024. The invention is ready to be translated for clinical and commercial application as the individual components of the proposed biomaterial vaccination platform have been approved for clinical trials and therapies. These components are aAPCs and various cytokines.
The publication: https://pubs.acs.org/doi/full/10.1021/acsnano.3c08559