Delivery System Optimization

Pure recombinant and synthetic antigens used in modern vaccines are generally less immunogenic than live/attenuated and inactivated whole organism vaccines. Scientists incorporate immunomodulators or adjuvants with modified delivery vehicles to improve the quality of vaccine production, including nanoparticles, liposomes, micelles and immune stimulating complexes (ISCOMs). Creative Biolabs has experts in formulation development. Our vaccines delivery optimization strategies can provide you with the best advice and accelerate your vaccine development program.

Delivery System

At present, there are many diseases for which the development of an effective vaccine is still difficult to achieve. In many cases, the vaccine was not successfully designed because the candidate failed to elicit the appropriate immune response. This is especially true where protective immunity requires cellular immunity, such as subunit vaccines. In the past decade, nanoscale sized (<1000 nm) materials such as virus-like particles (VLP), liposomes, ISCOMs, polymers and micelles have drawn attention as potential delivery vehicles for vaccine antigens. These delivery systems both stabilize vaccine antigens and act as adjuvants, some of which are able to enter antigen-presenting cells through different pathways and thus modulate the immune response to the antigen. This may be crucial for inducing a protective Th1-type immune response to intracellular pathogens. These properties also make them suitable for delivery of antigens on mucosal surfaces and intradermal administration.

Delivery System Optimization

Fig.1 Schematic representation of different nanoparticle delivery systems. [1]

Vaccines delivery systems allow for the incorporation of antigen doses so that boosting doses are no longer necessary as the antigens are slowly released in a controlled manner. A successful delivery system should have the following properties:

  • Protect antigen from degradation;
  • Sustain release of antigen;
  • Intracellular delivery of antigen contributing to cytotoxic T-cell stimulation and targeting at APCs.

Liposomes

Since the discovery of liposomes in 1965, they have been extensively studied as vaccine delivery systems. Liposomal vaccine delivery systems consist of nano- or micro-size vesicles, consisting of bilayers of phospholipids in which biologically active molecules are encapsulated, adsorbed or surface-coupled. Liposomes are generally not immunogenic by themselves, and therefore often combined with immune stimulatory ligands (adjuvants) or various other formulations as vaccine delivery systems.

Advantages:

  • Adapted to any antigen. From the entire pathogen (live attenuated or inactivated) to solubilized antigen fragments, whether hydrophilic or hydrophobic;
  • Easily modified. The size, charge, lipid composition and surface of liposomes can be easily modified to produce the desired immune responses to a particular antigen;
  • Long-lasting immune responses. Liposomes can mimic the pathogens and generate potent long-lasting immune responses.
Delivery System Optimization

Fig.2 Various modes of liposome–antigen association. [2]

Micelles

Peptide amphiphilic micelles are a class of biological materials that have unique potential as both self-adjuvants and vaccine delivery vehicles. Micelles are core-shell nanoparticles that spontaneously self-assemble in water to form single amphiphilic (hydrophobic/hydrophilic) molecules. Micelles have been used as drug delivery vehicles, and recently micellar nanoparticles have been explored as very valuable adjuvants for vaccine delivery by encapsulation/protection of hydrophobic drugs in the core of the micelles.

Advantages:

  • Small size (<100 nm). Micelles help deliver antigens to antigen-presenting cells (APCs) in draining lymph nodes, such as dendritic cells (DCs). These micelles are not only associated with DCs at the injection site but also target DCs by traveling through lymphatic vessels to lymph nodes to promote germinal center formation.
  • Easily display suitable surface properties (nature, surface charge) by selecting the appropriate micellar corona biocompatible hydrophilic fragments.
  • Through appropriate chemical design of hydrophobic and hydrophilic blocks, various other immunostimulatory molecules can readily be incorporated into these systems in a controlled manner to induce enhanced activation of DCs.

Delivery System Optimization

Fig.3 Schematic representation of the micellar nanoparticles developed as vaccine adjuvants [3]

The promising micelles have significantly improved the field of vaccine engineering. These systems are capable of exhibiting high and controlled immune response through appropriate chemical modification (appropriate surface charge, adjustable size, pH sensitivity, and reactive groups for antigen peptide / immune-stimulatory molecule immobilization, etc.). Indeed, there is room for improvement of micelles use as vaccine carriers for human vaccines, but they are still competitive candidates for vaccine delivery.

Adjuvants can improve the effectiveness of vaccines by promoting the immune response with a longer duration, increase the low response rate of some individuals and reduce the cost of vaccination programs by reducing the quantity of antigen needed. Delivery systems concentrate the adjuvant and antigens in repetitive patterns, target vaccine antigens to APCs and help co-localize antigens and immunopotentiators. Together, adjuvants and delivery systems can enhance body specific and active immune reaction.

Creative Biolabs offers expert consultation on vaccine delivery optimization strategies and detailed delivery plans. Working with our global network of technical, scientific and regulatory scientists provides you with the right expertise in the vaccine development process to boost efficiency, productivity, and profitability.

References

  1. Gregory AE; et al. Vaccine delivery using nanoparticles. Front Cell Infect Microbiol. 2013, 3: 13.
  2. Giddam AK; et al. Liposome-based delivery system for vaccine candidates: constructing an effective formulation. Nanomedicine (Lond). 2012, 7(12): 1877-93.
  3. Trimaille T; et al. Micelle-Based Adjuvants for Subunit Vaccine Delivery. Vaccines (Basel). 2015, 3(4): 803-13.

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