Configurable Adjuvant Development Opens the Door for a Galaxy of Improved Vaccines
Molecular structure of aluminum hydroxide, the oldest and most common adjuvant added to vaccine formulations. Image source: Wikimedia
With the renaissance of vaccines in full swing, advancements in adjuvant development are especially interesting. Traditional adjuvants such as alum have served effectively for decades1, but a new review has made the case that the age of disease-specific adjuvants is nigh as a result of chemically tailorable immunogenic adjuvant structures aimed at use in oral vaccination.2 By tailoring the adjuvant to the disease the vaccine is targeting, a stronger immune response is guaranteed, and so many previously untouched diseases can be vaccinated against.
The promise of tailorable adjuvants goes beyond the core issue of vaccine immunogenicity. Currently, alum is used as the adjuvant in the overwhelming majority of vaccines in the US, and its inclusion in vaccine products is taken for granted.3 Once researchers can generate their own alternatives to alum, rapid prototyping and testing of adjuvants is possible, adding to the already substantial number of variables involved in vaccine development. By introducing an additional variable to vaccine development, tailorable adjuvants promise greater efficacy in exchange for increased complexity. This means a powerful informatics suite which can handle this new aspect of vaccine design will be necessary.
Tailorable Adjuvants Means Tailorable Delivery
Tailorable adjuvants will disrupt oral vaccine delivery systems. With control over the structure of the vaccine’s adjuvant comes control over its delivery method and thus the ability of the vaccine to cross mucosa and cell barriers. Increased ability to survive the gastrointestinal tract means that the vaccine’s load of antigens or genetic material will arrive more efficiently at their final destination. Vaccines made using tailored adjuvants will be cheaper, more efficient, have fewer side effects and elicit stronger responses from effectors than traditional vaccines.4
The power and efficiency of a configurable adjuvant platform has an important catch. Unlike traditional vaccine adjuvants, generating disease-tailored adjuvants will become an additional step within the vaccine development pipeline. In order to handle the design, testing and implementation of tailorable adjuvants, vaccine developers will need a software package that can match their new needs.
Generating prototypes of tailored adjuvants requires:
- Defining the desired downstream immune response by modeling activity by effector cells
- Mapping and simulating the relevant cells at each point in the vaccine’s journey through the body
- Defining the structure of the tailored adjuvant based off the method of administration and chemical properties of the antigen
- Examining interactions between the adjuvant and other components of the vaccine
- Simulating the tailored adjuvant and antigen complex, ensuring that there is no contradictory biochemistry or blocked binding domains
- Modeling the interactions between the tailored adjuvant and mucosa and cell membranes
- Modeling the binding of the adjuvant to effector receptors
- Assessing off-target binding to the vaccine complex
- Modeling the tailored adjuvant’s degradation while at the target site
- Planning and executing chemical reactions to create the tailored adjuvant which was designed
These steps rely on robust simulation of biochemical interactions as well as bigger picture physiological effect tracking. Understanding the localization of the vaccine to the target tissue and the adjuvant’s impact on antigen processing will be critical to developing tailored adjuvants. Mapping of the tailored antigen’s intended mechanism of action will be a necessary feature of vaccine design software.
The Next Generation of Vaccine Development
As tailorable adjuvants become more common, they will likely be paired with other members of the new generation of adjuvants which make use of immunogenic small molecules.5 As using multiple adjuvants in conjunction with each other becomes more common, the vaccine design process is complicated even further. Unlike with traditional adjuvants, a variety of safety and efficacy experiments will be required for vaccines developed with tailored adjuvants.
Once generated after design, the tailorable adjuvants of the future will also need to test:
- Antigen delivery to immune cells
- Vaccine passage through GI tract
- Immunogenicity of adjuvant itself
- Immunogenicity of antigen alone
- Adjuvant-adjuvant interactions during passage through mucosa
- Duration of immune memory after vaccination
- Strength of immune response after challenge
- Cellular and tissue inflammation
- Durability of immune response
Many software suites have elements of the needed design suite under one roof, but few provide a unified solution on a common platform. Having a unified design and informatics solution will go a long way to simplify dealing with the many variables required to rapidly prototype vaccines using tailorable adjuvants. There are a number of software requirements that are specific to vaccine design of this type:
- In silico design and analysis of the tailored adjuvant itself
- In silico safety and efficacy testing of the adjuvant
- Formulation variant data tracking
- Side effect and inflammation prediction
- Vaccine elimination prediction
- Tracking of immune challenge timepoints and boosters
- Tracking of adjuvant inventory and efficacy
- Robust collaboration and analysis
Without powerful software to design and test tailorable adjuvants, it’s unlikely that researchers will be able to move the next generation of super-effective vaccines to the clinic. The new generation of vaccine design requires an intense laboratory informatics solution that is able to handle pre-experimental biochemical modeling as flawlessly as experimental results. For a mandate as large as vaccine design, there is only one software suite of superior quality and breadth.
BIOVIA’s Designed to Cure is the software platform that can unite the design and implementation features required to develop next generation vaccines with tailored adjuvants. Using Designed to Cure, vaccine development will be massively simplified by having adjuvant design, vaccine design, and the subsequent experimental data managed under one roof. Contact us today to find out how BIOVIA can help you get the most out of the latest research and move science forward.
- “Vaccines with Aluminum-Containing Adjuvants: Optimizing Vaccine Efficacy and Thermal Stability.“ February 2011, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201794 ↩
- “Chemical Synthesis, Versatile Structures and Functions of Tailorable Adjuvants for Optimizing Oral Vaccination.“ December 2016, http://pubs.acs.org/doi/full/10.1021/acsami.6b10470 ↩
- https://www.cdc.gov/vaccinesafety/concerns/adjuvants.html ↩
- “New Generation Vaccine Adjuvants.” April 2007, http://www.roitt.com/elspdf/Newgen_Vaccines.pdf ↩
- “Rational design of small molecules as vaccine adjuvants.” November 2014, http://stm.sciencemag.org/content/6/263/263ra160 ↩