Subunit vaccine production

The basic process technology in vaccine production consists of fermentation for the production of antigen, purification of antigen, and formulation of the final vaccine. In bacterial fermentation, technology is weU estabHshed. For viral vaccines, ceU culture is the standard procedure. Different variations of ceU line and process system are in use. For most of the Hve viral vaccine and other subunit vaccines, production is by direct infection of a ceU substrate with the vims. 

Awram, P., et ah. The potential of plant viral vectors and transgenic plants for subunit vaccine production. Adv Vims Res, 2002 58 81-124. 

Alternatively, some subunit viral vaccines can be generated by rDNA techniques and expressed in a continuous ceU line or insect ceUs. Recent advances in bioreactor design and operation have improved the successful production of IPV in large-scale bioreactors. However, roUer bottles or flasks are stiU used for most current vaccine production. Development of insect ceU culture will allow for very large-scale Hquid suspension culture (143). Several vaccine candidates such as gpl60 for HIV and gD protein for herpes have been demonstrated in the insect ceU culture system. However, no vaccine has been approved for human use. 

Conventional pharmaceutical development has been estimated to costs roughly between 100 million and 800 million per product, and takes over 12 years. The development of conventional vaccines may be somewhat less costly, although new recombinant DNA-derived subunit vaccines produced in fermentation-based systems are likely to be similar to protein pharmaceuticals in development costs. At present, none of the major pharmaceutical companies is directing funding towards the development of plant-derived vaccines for infectious diseases. This may reflect ... 

In order to overcome environmental concerns in particular, some companies are investigating the use of engineered plant cell lines as opposed to intact transgenic plants in the context of biopharmaceutical production. One company (DowAgroSciences) gained approval in 2006 for a veterinary subunit vaccine against Newcastle disease in poultry produced by such means. 

The advent of recombinant DNA technology has rendered possible the large-scale production of polypeptides normally present on the surface of virtually any pathogen. These polypeptides, when purified from the producer organism (e.g. E. coli, Saccharomyces cerevisiae) can then be used as subunit vaccines. This method of vaccine production exhibits several advantages over conventional vaccine production methodologies. These include ... 

Production of subunit vaccine in an unlimited supply. Previously, production of some vaccines was limited by supply of raw material (e.g. hepatitis B surface antigen see below). 

A number of such recombinant (subunit) vaccines have now been approved for general medical use (Table 13.9). The first such product was that of hepatitis B surface antigen (rHBsAg), which gained marketing approval from the FDA in 1986. Two billion people are infected with hepatitis B worldwide, 350 million individuals suffer from life-long chronic infection, and more... 

An alternative approach to the production of subunit vaccines entails their direct chemical synthesis. Peptides identical in sequence to short stretches of pathogen-derived polypeptide antigens can be easily and economically synthesized. The feasibility of this approach was first verified in the 1960s, when a hexapeptide purified from the enzymatic digest of tobacco mosaic virus was found to confer limited immunological protection against subsequent administration of the intact virus. (The hexapeptide hapten was initially coupled to bovine serum albumin, used as a carrier to ensure an immunological response.)... 

Not withstanding the possible value of such inactivated viral vaccines, the bulk of products assessed to date are subunit vaccines. Live vector vaccines expressing HIV genes have also been developed and are now coming to the fore (Table 13.12). 

Most of the recombinant subunit vaccines tested in the first half of this decade employed gp 120 or gp 160 expressed in yeast, insect or mammalian (mainly CHO) cell lines. Eukaryotic systems facilitate glycosylation of the protein products. Like all subunit vaccines, these stimulate a humoral-based immune response but fail to elicit a strong T-cell response. The failure to elicit a cell-based... 

Expression of Potential Vaccine Antigens. In general, in the future, eukaryotic cell culture is likely to be the method of choice for the production of subunit vaccine antigens where the organism to be vaccinated against replicates in eukaryotic cells. E. coli are unable to posttranslationally modify some vaccine candidates for example, bacterial systems cannot add carbohydrate which is important in the antigenicity and structure of many protective antigens. 

Improved safety is the primary advantage of subcellular and subunit vaccines over whole-killed vaccines. Because the pathogen itself is not used as the source material, vaccines manufactured by recombinant DNA technologies provide a greater margin of safety. Production of... 

The genetic engineering of hepatitis subunit vaccine in yeast cells has resulted in a subunit vaccine replacing the conventional whole cell vaccines obtained from the plasma of infected humans. The main advantages of recombinant DNA (rDNA) vaccines when compared with human plasma products is that they offer higher yields, are of more consistent quality, and are safer, thereby being easier to produce and cheaper. 

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