Vaccines purified subunit

Vaccination to induce an adaptive immune response is expected for a broad range of infectious diseases and cancers. Traditional vaccines are mainly composed of live attenuated viruses, whole inactivated pathogens, or inactivated bacterial toxins. In general, these approaches have been successful for developing vaccines that can induce an immune response based on antigen-specific antibody and cytotoxic T lymphocyte (CTL) responses, which kill host cells infected with intracellular organisms (Fig. 1) [1,2], One of the most important current issues in vaccinology is the need for new adjuvants (immunostimulants) and delivery systems. Many of the vaccines currently in development are based on purified subunits, recombinant... 

Garcon N, Heppner DG, Cohen J. Development of RTS,S/AS02 a purified subunit-based malaria vaccine candidate formulated with a novel adjuvant. Expert Rev Vaccines 2003 2 231-8. 

Uncertain. If an interaction occurs, it has been suggested it is probably due to inhibition of the liver enzymes concerned with the metabolism of theophylline, possibly secondary to interferon production, resulting in theophylline accumulation in the body. - One suggestion is that vaeeine contaminants, which are potent interferon-inducing agents, may be responsible (rather than the vaccine itself), so that an interaction would seem to be less likely with modem highly-purified subunit vaccines. In one study where an interaction occurred, an increase in seram interferon levels was detected, whereas, in two of the studies showing no interaction, no interferon production was detected. " Influenza infection per se can result in decreased theophylline clearance and theophylline toxicity. "... 

Winstanley PA, Tjia J, Back DJ, Hobson D, Breckenridge AM. Lack of effect of highly purified subunit iiifiuent vaccination on dieophyUme metabolism. BrJ Clin Pharmacol (1985) 20,47-53. 

A logical extension of the use of purified subunit vaccines is to try to produce antigenic components which are capable of producing an immune response using biotechnology. The first successful example of this was the hepatitis B subunit vaccine which has been very successful. The production of this is described in detail below. 

Vaccine candidates are based on the two viral surface proteins, gD and gB (80). Recombinant methods are used to express the proteins, either in Chinese hamster ovary (CHO) cells or in baculovims. The proteins are purified as subunits and formulated with different adjuvants. Clinical trials with these vaccine candidates have been performed, but the results to date have not been encouraging. 

To identify and characterize bacterial and viral antigens which can then be purified and used to prepare subunit vaccines. 

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 ... 

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.)... 

Engerix B (tradename) is a subunit vaccine containing purified recombinant hepatitis B surface antigen (HBsAg) that gained approval in the USA in 1998. It is indicated for active immunization against infection caused by all known serotypes of hepatitis B virus. 

Subunit vaccines Immunogenic proteins or peptide antigens customized to specific antigenic determinants are purified from tissue culture HIV, rabies virus, influenza virus, hepatitis B virus... 

Although there are a number of advantages associated with the use of subunit vaccines (e.g., highly purified peptides, proteins or DNA) as vaccines (e.g., specificity), one feature they all have in common is that they are generally poorly immunogenic. The more traditional vaccines contain many other components, some of which elicit additional T-cell assistance or function as adjuvants. An adjuvant is a substance that acts as an immunostimulator, one example being the bacterial DNA in a whole cell vaccine. The overall result is a more robust immune response than that provided by the antigen alone. 

A subunit vaccine consists of one or more immunogenic epitopes, proteins, or other components of a pathogenic organism. Immunogenic epitopes can be chemically synthesized and are known as peptide vaccines, e.g., peptide vaccine candidates for foot-and-mouth disease virus. The pathogen could be disrupted, and one or more immunogenic proteins such as bacterial cell wall proteins flagella or pili and viral envelope, capsid, or nucleoproteins can be purified. The isolation of such components in purified form is sometimes cumbersome and expensive. However, bacterial exotoxins can be easily purified, inactivated, and used as toxoid vaccines. 

Influenza vaccine viruses are propagated in embryonated chicken eggs. The virus-containing extra-embryonic fluid is harvested, purified, and inactivated with formalin. Inactivated flu vaccine is produced either as whole virus vaccine or ether-disrupted split or subunit preparations. However, many other new or modified influenza vaccines are already available or are expected to appear in the near future, for example vaccines containing new adjuvants, live attenuated vaccines, and vaccines administered by alternative routes. 

Vaccine production is pursued with the objectives to genetically engineer vaccines with specific gene deletions reducing virulence produce viral and bacterial vectored vaccines and develop subunit vaccines using purified antigens obtained from in vitro expression vectors such as pseudorabies purified protein vaccine and foot-and-mouth disease vaccine. 

The reader wUl have noted that many production aspects for existing vaccines are quite archaic. This is so because most vaccines were developed before the biotechnology revolution, which is creating a generation of highly purified and better-characterized subunit vaccines. As such, for older vaccines the process defines the product, and process improvements cannot readily be incorporated into these poorly characterized vaccines without extensive new clinical trials. With improved scientific capabilities, we can... 

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