Development of a microfluidic-based platform for delayed vaccine delivery

Vaccination is one of the most cost-effective medical interventions in the treatment of various infectious diseases. The impact vaccines have had on overall mortality since their formal introduction has not been equalled by any other medical intervention to date. Yet, each vaccination requires the respect of a strict schedule of injection to generate an effective protection. Vaccines compliance is crucial, and not always easy to achieve, particularly in developing countries where the lack of access to public health-care services and the lack of health follow-up break the establishment of a world global immunity protection through vaccination.
Thus, creating a formulation able to avoid the need of booster vaccination would lead to a significant improvement in the whole world vaccination coverage, without any concerns about respect of the vaccination schedule. In this purpose, investigations have been made on microparticles of biopolymers encapsulating the vaccine. These biopolymers would surround the antigen, creating a shell that would degrade slowly in the body, ideally releasing the vaccine in the right timing, thus mimicking the booster vaccination. However, there are several barriers on the way of the development of a technology platform able to encapsulate any vaccine and provide the aimed kinetic of release in vivo and my research are focused on overcoming these obstacles.

First the production of microcapsule forming a polymer shell around a core containing the vaccine is a challenge, as the microparticles need to be consistent in size, chemical and biological properties, and antigen loading. Classic methods to produce microparticles involve rough stirring that results in polydispersed particles with a low yield of encapsulation. Thus, it is inconceivable to inject particles where the quantity of vaccine varies from patient to patient. However, microfluidics technology could provide methods to solve this issue. Microfluidics is the manipulation of flows at a microscopic scale, where the fluids act differently, with different physical properties compared to the macroscopic world. This different fluid behaviour can be utilised to create monodispersed and fully loaded core shell particles being able to release their full and intact content although it requires tests and development of the microfluidic encapsulation process as the first part of this thesis.

The other main part of the project is to determine the correct formulation of polymer and vaccine to generate the adequate kinetic release without damaging the vaccine or reducing is efficiency. It will involve studies on the chemistry and pharmacology of the material used for this purpose, in vitro release assay and modelling using different mathematical models.

Although the project aims to create a general delivery technology compatible with every vaccine, a Proof of Concept in-vivo in mice will finally be performed with ovalbumin, to assess the safety, biodistribution of the particles and their ability to deliver the booster in a delayed manner. The timing of release in-vivo and in-vitro will be compared to enable prediction of release for different formulations.

More generally, the creation of a single dose vaccine would be a major step in the establishment of a world global immunization, helping to comply with any vaccine schedule.