Nanovaccines: Current Advances and Challenges

Nanotechnology has revolutionized vaccine development in medical research, ushering in significant advancements. Nanovaccine technology, with its unique advantages and immense potential, has attracted global attention from researchers. This article provides a clear and concise overview of the working principles, characteristics, types, application areas, current development status, and future prospects of nanovaccines.

Basic Principles of Nanovaccine Technology

Nanovaccines combine key vaccine components (such as antigens and adjuvants) with nanomaterials to create nanoparticles with specific structures and functions. These nanoparticles are tiny, typically ranging from 1 to 1000 nanometers, and their effectiveness relies on the unique properties of nanomaterials and the recognition mechanisms of the immune system.

When nanovaccines enter the body, their small size allows them to easily cross physiological barriers and be efficiently captured by antigen-presenting cells (such as dendritic cells and macrophages). This process involves various cellular uptake mechanisms, such as endocytosis and phagocytosis, ensuring the intracellular delivery and effective processing of antigen components within the nano vaccine. These antigens are then finely processed and presented to the immune system, triggering robust cellular and humoral immune responses.

Moreover, nanomaterials act as "guardians" of the vaccine components, effectively protecting them from degradation and clearance within the body, thereby extending their functional duration. By designing nanoparticles' surface characteristics and structure, researchers can achieve precise targeted delivery of the vaccine, greatly enhancing its concentration and therapeutic effect at specific sites.

Characteristics of Nanovaccine Technology

Enhanced Immune Response

Nanovaccines effectively activate the immune system, producing a stronger and longer-lasting immune response. This is primarily due to the efficient uptake and antigen presentation by nanoparticles. These particles can mimic the size and shape of pathogens, making them more easily recognized as foreign invaders by the immune system, thus triggering a strong immune response. Additionally, nanoparticles can concentrate antigens and deliver them directly to antigen-presenting cells, facilitating antigen processing and presentation, and activating T cells and B cells to produce high levels of antibodies and cellular immune responses.

Targeted Delivery

By modifying the surface of nanoparticles, they can be engineered to target specific cells or tissues. For example, using molecules like antibodies or ligands to modify the surface of nanoparticles allows them to specifically bind to receptors on the surface of target cells, achieving precise targeted delivery. This targeted delivery increases the concentration of the vaccine at the specific site, reduces distribution to non-target areas, minimizes side effects, and enhances therapeutic effectiveness.

Slow Release and Long-Lasting Effect

Nanoparticles can serve as reservoirs for drugs or antigens, enabling slow release and long-lasting effects. By selecting appropriate nanomaterials and preparation techniques, the release rate of drugs or antigens from nanoparticles can be controlled, allowing for sustained release in the body. This maintains prolonged immune stimulation, reducing the number of vaccinations needed and improving patient compliance.

Improved Stability

Nanovaccines effectively protect vaccine components from external environmental factors such as temperature, pH, and enzymes. This helps extend the shelf life of vaccines, making them easier to store and transport. This is particularly significant for vaccine components that are unstable at room temperature, as the application of nanotechnology enhances their stability.

Combined Immunotherapy

Nano vaccines can be combined with other immunotherapy methods, such as immune checkpoint inhibitors and cytokines, to achieve synergistic effects and improve therapeutic outcomes. For example, using nano vaccines in conjunction with immune checkpoint inhibitors can relieve the suppression of the immune system, enhancing the ability of immune cells to attack tumor cells.

Types of Nanovaccines

nanovaccines-types

Figure 1. Types of nanoparticle vaccines [1]

Polymeric Nanovaccines

Polymeric nanomaterials such as Poly(lactide-co-glycolide) (PLGA), poly(ε‐caprolactone), and chitosan, have excellent biocompatibility and biodegradability. By methods such as emulsification and solvent evaporation, antigens can be encapsulated inside polymer nanoparticles to form polymer nanovaccines. Polymer nanoparticles can control the rate of antigen release and can be surface-modified for targeted delivery and immunomodulation.

Lipid-Based Nanovaccines

Lipid-based nanovaccines, particularly those using lipid nanoparticles (LNPs), are a promising approach in vaccine development due to their modularity, flexibility, and ability to preserve and present conformational epitopes to antigen-presenting cells (APCs), inducing neutralizing antibodies. Liposomes, composed of phospholipid bilayers, can carry both hydrophilic and hydrophobic drugs, DNA, and RNA, offering high loading capacity, targeted delivery, good biocompatibility, and effective cargo protection. Encapsulating antigens in liposomes enhances antigen-specific B cell responses compared to soluble antigens. To address the susceptibility of conventional LNPs to enzymatic and immune degradation, combining lipids with polymers like polyethylene glycol (PEG) has proven effective, enhancing transport across the blood-brain barrier and protecting mRNA during cellular delivery.

Self-Assembling Peptide/Protein Nanovaccines

Peptides and proteins that self-assemble into nanostructures like hydrogels, nanoparticles, and nanofibers are emerging as a promising vaccine design strategy. These nanomaterials can be precisely engineered to control structure, assembly, and epitope content. Supramolecular peptide nanofibers can modulate immune responses and facilitate antigen transport through mucosal barriers. Injectable hydrogels, β-sheet nanofibers, and multivalent nanoparticles offer tailored immune responses.

Biomimetic Nanovaccines

Biomimetic nanomaterials include virus-like particles, cell membrane-coated nanoparticles, and extracellular vesicles. They can mimic the structure and function of biological entities, offering the potential to enhance immunogenicity and safety.

Inorganic Nanovaccines

Inorganic nanomaterials include gold nanoparticles, quantum dots, and carbon nanotubes. They can trigger inflammatory responses, promote macrophage activation, and enhance T-cell polarization, thereby boosting the immune response.

Applications of Nanovaccine Technology

Infectious Diseases: Nanovaccines can enhance immune responses against various viruses (such as SARS-CoV-2, HIV, and influenza) and bacteria/parasites (such as HCV, RSV, malaria, and TB). This can be achieved using mRNA nanoparticles, virus-like particles, self-assembling nanoparticles, and exosomes.

Cancer: Nanovaccines can deliver tumor-associated antigens, triggering immune responses against tumors and potentially enabling personalized treatments. This includes the use of peptide nanofibers, cell membrane-coated nanoparticles, DNA nanostructures, and RNA nanoparticles.

cancer-nanovaccines

Figure 2. Anticancer nanomaterial vaccine platforms [1]

Inflammatory Diseases: Nanovaccines can be used for active immunotherapy, stimulating the host immune system to produce immune responses against pathogen self-antigens, such as using Q11 self-assembling peptide nanofibers. Additionally, nanovaccines can induce antigen-specific tolerance to treat inflammatory responses in autoimmune and allergic diseases. This is achieved through the use of PLGA nanoparticles, nanoemulsions, and exosomes.

Allergic Diseases: Nanovaccines can deliver allergens and induce tolerance, thereby reducing allergic reactions. This can be done using PLGA nanoparticles, virus-like particles, and lipid nanoparticles.

Challenges of Developing Nanovaccines

Limited understanding of the interface between nanomaterials and innate and adaptive immune cells: More in-depth research is needed to understand how nanomaterials interact with the immune system and how they influence immune responses. This includes studying their biodistribution, long-term efficacy, and clearance pathways.

Scalability of Nanovaccines: There is a need to improve the manufacturing processes of nanoparticle-based vaccines to facilitate large-scale production and reduce costs.

Personalized Nanovaccines: Using computational methods like artificial intelligence, personalized nanovaccines can be developed for immunotherapy targeting specific neoantigens in patients.

Equitable Vaccine Distribution: Developing nanomaterial platforms that do not require ultra-low temperature cold chains and needle-free delivery systems can improve vaccine equity and accessibility.

Future Prospects

Development of Nanovaccines: Efforts will focus on creating more effective, safer, and easier-to-produce nanovaccines. This includes optimizing the structure and properties of nanomaterials, improving manufacturing processes, and utilizing computational methods for vaccine design.

Applications of Nanovaccines: Expanding the use of nanovaccines to a broader range of diseases, such as cancer, inflammatory diseases, and autoimmune disorders.

Social Impact of Nanovaccines: Enhancing vaccine accessibility and equity, thereby promoting global health.

Nanovaccines hold immense potential in vaccine development, addressing the limitations of current vaccine technologies and paving the way for personalized treatments. In the future, nanovaccines will play a crucial role in combating infectious diseases, cancer, and inflammatory conditions.

References:
[1] Shetty S, Alvarado PC, Pettie D, Collier JH. Next-Generation Vaccine Development with Nanomaterials: Recent Advances, Possibilities, and Challenges. Annu Rev Biomed Eng. 2024 Jul;26(1):273-306. doi: 10.1146/annurev-bioeng-110122-124359. PMID: 38959389.