The project

Rationale and Impact of MACIVIVA

With few exceptions, commercialized vaccines are generally delivered by injection through the intramuscular or subcutaneous route. Vaccines contain immunogens classically found within a large variety of biological compounds such as peptides, proteins, glycoproteins and sometimes carbohydrates and lipids. These immunogens may trigger the immune system for producing antibodies and/or cytotoxic T cells for preventing the pathogen transmission or blocking and/or slowing down the disease progression.

However, these vaccines generally exist as liquid formulation that are inherently prone to physical and/or chemical modifications. The cold chain storage is still fundamental for preserving the bioactivity of most liquid and freeze-dried vaccines. For reconstituted freeze dried vaccines, they harbor important instability and must be used within hours and kept refrigerated. Vaccine degradation generally takes place during shipment and/or storage of liquid or lyophilized products, which may affect the immunological properties of the immunogens, with unwanted immune responses or insufficient immune protection. There is growing evidence that solid dosage formats (e.g. powder form) for vaccines may offer several advantages over the liquid formulations, such as the prevention of molecular motion and shear-induced degradation, and slowing down modifications and degradation reactions involving water and oxygen radicals, resulting in improved stability, enhanced shelf-life of vaccines and greatly simplified logistics.

Toward cold chain free vaccines

Today, no commercial vaccine has been developed yet under thermostable solid form (cold chain independent) for direct nasal or oral delivery (ex. intranasal powder delivery or sublingual pills) without the need of reconstitution with a liquid.

Many regions of developing countries also lack electricity or have no refrigerator/freezer for keeping vaccines below 4-8oC. The development of cold-chain independent vaccines under solid powder forms that could be administered through non-invasive routes (needle-free immunization) may represent the long-term global solution to the vaccination challenges. Upscale production of such solid form vaccines would be relatively inexpensive, easy to administer and it could improve National Immunization Programs, especially in the developing world but also in developed countries in Europe. Such solid form vaccines could also offer improved safety and compliance, decreasing costs, and reducing pain associated with vaccinations.

Needle-free immunization through mucosal surfaces (mouth, nose, lungs, intestinal or genital tract) might also reduce the risk of infection from HIV, hepatitis, and other serious diseases due to the use of unsterilized needles, and it may also improve the front line protection at the mucosal levels against mucosally transmitted pathogens such as HIV, influenza, rotavirus.

The development of a robust “universal-like” manufacturing process for obtaining thermostable virosome dried powder by spray drying (heat drying) or lyophilization (freeze drying) might open the doors to novel vaccine formulations. In the future, this may allow the manufacturing of multiple human safe needle-free virosome-based vaccines that could be self-administered directly to the subject through the following non-invasive routes: Intranasal, oral and sublingual, without the need of vaccine reconstitution with a liquid solution. MACIVIVA may potentially pave the path to other large scale thermostable nanopharmaceuticals products for therapeutic and prophylactic vaccines and other potential applications for direct application by non-invasive routes.

Virosomes are virus-like particles

Virus-like particle (VLP) based vaccines are biodegradable and have very good safety tract records for human use. They are formed by self-assembly of biocompatible proteins forming nanoparticles, lacking infectious nucleic acid. VLPs can be derived from a variety of viruses, with sizes generally ranging from 20 nm to 300 nm, and can be manufactured with a variety of process technologies.

By the nature of nanoparticle size and repetitive structural order, VLPs induce potent immune responses, even in the absence of adjuvant. VLP based vaccines are the first nanoparticle class to reach the market in 1986. These vaccines have paved the path to new VLP-based vaccines and today, non-invasive routes are becoming more attractive due to technology evolution. The VLP vaccine approach is now subdivided into two types: The non-enveloped VLPs made of proteins and enveloped VLP harboring lipid membranes with protein anchored at the surface, as the influenza virosomes used in this MACIVIVA project.