Vectors vaccines

Most vaccine vectors developed to date are viral based, with poxviruses (as well as picorna viruses and adenoviruses) being used most. In general, such recombinant viral vectors elicit both 

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. 

The protective efficacy of Engerix B has been demonstrated in a number of trials, in the context of infants, children and adults. Seroprotection rates (measured as serum anti-hepatitis B antibody titres above a value of 10 mlU ml-1) of over 95 per cent were usually recorded. The product was found to be generally well tolerated. The most frequently reported adverse effects were local reactions at the injection sites, fever, headache and dizziness. Special consideration to risk benefit ratio should be given to MS patients, as exacerbations of this condition have been (rarely) reported following administration of hepatitis B and other vaccines. Engerix B is manufactured and marketed by GlaxoSmithKline. 

A number of factors render vaccinia virus a particularly attractive vector system. These include  

Removal of pathogen gene and incorporation into vector genome 

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Live vectors (131,133) are another appHcation of genetic engineering. In this case, the genes from a pathogen are inserted into a vaccine vector, such as salmonella or vaccinia. In the case of salmonella, it will be possible to develop an oral vaccine. Vectors for this appHcation include salmoneUa, BCG, poHo, adenovims, and vaccinia. 

Vaccine vector now expressing pathogen surface antigen... 

Figure 13.12 Strategy adopted for the development of an engineered vaccine vector. Refer to text for additional detail...

Andino, R. et al. (1994). Engineering poliovirus as a vaccine vector for the expression of diverse antigens. Science 265, 1448-1451. 

Killeen, K., D. Spriggs, and J. Mekalanos, Bacterial mucosal vaccines Vibrio cholerae as a live attenuated vaccine/vector paradigm. Curr Top Microbiol Immunol, 1999. 236 237-54. 

Vaccine Vectors being Developed for Intravaginal Immunization... 

Easier to manufacture than other vaccine vector types... 

A range of different vaccine vectors has been developed over time to provoke an immune response within the body [127,142], However, it has only been comparatively recently that they have been applied to inducing mucosal immunity within the uterovaginal tract. The general vector platforms that have been used include attenuated viruses, live viruses, commensal bacteria, DNA vectors, and protein subunit/peptide or virus-like particles (Table 21.9). The choice of vector is dependent on a number of factors such as the pathogenic virus and bacterial type and the length of duration of immunity required. 

Walsh (2003) defined biopharmaceuticals as therapeutic protein or nucleic acid preparations made by techniques involving recombinant deoxyribonucleic acid (DNA) technology. Therapeutic proteins include blood clotting factors and plasminogen activators, hemopoietic factors, hormones, interferons and interleukins, and monoclonal antibodies (LeVine, 2006). Over time, the term biopharmaceutical has broadened, and, in addition to proteins and nucleic acids, now includes bacteriophages, viral and bacterial vaccines, vectors for gene therapy, and cells for cell therapy (Primrose and Twyman, 2004). Attention here focuses on proteins, since the majority of approved biopharmaceuticals are proteins. 

Vaccine adjuvants Vaxjo Vaccine vectors www.violinet.org/vaxjo Adjuvants and related vaccines... 

Vaxvec www. violinet. org/vaxvec Vaccine vectors database... 

As a manufactured product, a vaccine is composed of several components. A vaccine antigen(s) is a required component for any vaccine. Such a vaccine antigen can be part of a whole organism (e.g., live attenuated vaccine), a protective protein antigen, or an immune epitope. A live attenuated vaccine usually does not require a vaccine adjuvant that functions as an immune stimulant. However, killed whole organism or subunit vaccines usually need vaccine adjuvants. Otherwise, a weak or nonexistent immune response will be induced. Other vaccine components include vaccine vectors and vaccine preservatives. Databases of these vaccine components are briefly introduced here. 

Tatsis N, Ertl HC. Adenoviruses as vaccine vectors. Mol Ther 2004 10 616-29. 

Oggioni, M. R., Medaglini, D., Maggi, T., and Pozzi, G. (1999), Engineering the grampositive cell surface for construction of bacterial vaccine vectors, Methods, 19, 163-173. 

Type of product and formulation, e.g. live or inactivated vaccine, vector vaccine, type of vector, liquid or lyophilized product, adjuvant, special formulations. 

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