Liposomes

A liposome is an artificially-prepared vesicle composed of a lipid bilayer. The liposome can be used as a vehicle for administration of nutrients andpharmaceutical drugs. Liposomes can be prepared by disrupting biological membranes (such as by sonication).

Liposomes are composed of natural phospholipids, and may also contain mixed lipid chains with surfactant properties (e.g., eggphosphatidylethanolamine). A liposome design may employ surface ligands for attaching to unhealthy tissue.

The major types of liposomes are the multilamellar vesicle (MLV), the small unilamellar vesicle (SUV), the large unilamellar vesicle(LUV), and the cochleate vesicle.

Virus-like-particles or virosomes

Virus-like particles (VLPs) and virosomes, have been developed depending on the nature of the viral pathogen to be targeted and the type of immune response (humoral vs cellular) to be elicited. Particulate structures allow the insertion or fusion of foreign antigenic sequences, resulting in chimeric particles delivering foreign antigens on their surface. Similarly, they are used as carriers for foreign antigens, including non-protein antigens, via chemical conjugation.

Antigens

In immunology, an antigen is a substance that evokes the production of one or more antibodies. Each antibody binds to a specific antigen by way of an interaction similar to the fit between a lock and a key. The substance may be from the external environment or formed within the body. The immune system will try to destroy or neutralize any antigen that is recognized as a foreign and potentially harmful invader. The term originally came from antibody generator

DNA vaccines & gene therapy (some animal vaccines, vaccines in development)

Gene therapy is related to vaccines, although the products are mostly intended for therapeutic use, and involves delivering DNA to the target cells in the body, allowing them to produce molecules the lack of which are implicated in genetic disorders, supplement immunity and many other potential treatments.

Production of correctly coded DNA (or RNA) strands for this purpose for use directly in patients, for incorporation into vectors, or into recombinant cells used to produce proteins that are the target product may be challenging, as the DNA molecules are large, strongly charged and often start off in high particulate, viscous solutions.

Polysaccharide vaccines and conjugates (ex. Hib and Pneumococcal vaccines)

The steps in the production of conjugate vaccines can be summarized as follows:

• Protein production:  fermentation of host organism, collect, wash, homogenize, recover and purify protein
• Polysaccharide production: fermentation of donor organism, disrupt cells, purify polysaccharide, trim by hydrolysis (acid, periodate)
• Derivativization: make both components reactive
• Conjugation: React components together
• Purification: Remove unwanted compounds
• Finish and fill: Concentrate to final strength, dialyse into appropriate solute, sterile fill as liquid or lyophilize

Recombinant Protein vaccines (ex. Hepatitis B and HPV)

Many vaccines are being developed based on the ability of proteins to invoke an immune response. Some traditional vaccines are protein toxoids, and modified toxoids are used in most conjugate vaccines to promote an immune response against the conjugated species, typically a polysaccharide.

Polysaccharide production has a similar set of unit operations, although there is either a size-exclusion chromatography (SEC) step to select for molecular weight class of the polysaccharide fragment, or this can be achieved using an ultrafilter cascade where the molecular weight species of interest is fractionated between two ultrafilters rated above and below the molecular weight desired. 10 KDa at the lower end and 100 KDa or 300 KDa at the upper end are often used. Tangential flow filtration (TFF) has advantages over SEC as the resulting product with selected molecular weight is not highly diluted as it may be with SEC, and may then require a further TFF concentration step.

Microbial vaccines and toxoids (ex. DTaP)

Microbial vaccines are most frequently comprised of the cell wall components that allow the immune system to recognize the whole organism, or in bacteria that cause disease through toxicity – such as Diphtheria, the toxin or derived toxoid may be used. Antitoxins are being developed for some disease organisms, predominantly for therapeutic use.
Bacteria may be cultured in liquid media, or as solid substrate cultures, harvested, purified and used directly as killed or attenuated vaccines.