Vaccine, Vector-based

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... 

Yeast expression vectors have been among those most commonly used since the beginning of gene technology. Vectors based on baker s yeast, Saccharomyces cerevisiae, have been especially popular for robust expression of many types of recombinant proteins [90]. For instance, the first commercially available recombinant vaccine, the hepatitis B surface antigen vaccine, was produced from an S. cerevisiae vector [91]. Many other recombinant proteins have also been efficiently expressed in yeast including al-Antitrypsin [92], insulin [93], Epstein-Barr virus envelope protein [94], superoxide dismutase [95] and interferon-a [90]. 

Advances in genomics, molecular biology, and recombinant technology have provided new directions for the discovery, development, and manufacture of vaccines. One of the current approaches is a minimalist strategy to decouple the virulence and immunity functions. The aim is to use only the immunity part to confer protection, so that the vaccine is safe to be administered. The approach can be divided into subunit, vector-based, DNA, and peptide vaccines. 

Vector-Based Vaccines Viruses and bacteria are detoxihed and used as vehicles to carry vaccines. Subunit vaccines are delivered by carrier vehicles to elicit the immune response. An example is the use of canarypox (a virus that infects birds, but not humans) to carry envelope proteins for HIV treatment. Multiple types of envelope proteins can be delivered with this method. Clinical trials with this type of vector-based vaccines are being investigated. 

J. Kuball, M. Schnler, E. Antunes-Ferreira, W. Herr, M. Neumann, E. Obenaner-Kntner, E. Westreich, C. Huber, T. Wolfel, and M. Theobald, Generating p53-specific cytotoxic T lymphocytes by recombinant adenoviral vector based vaccination in mice bnt not man. Gene Therapy, 833-843 (2002). 

Several HIV vaccine systems based upon live vectors have also been developed, in an attempt to stimulate a significant T cell as well as B cell immune response. Both envelope and core antigens have been expressed in a number of recombinant viral systems, most notably in vaccinia. The clinical efficacy of these remain to be established. 

Fattori E, Zampaglione I, Arcuri M,Meola A, Ercole BB, Cirillo A,Folgori A, Bett A, Cappelletti M, Sporeno E, Cortese R, Nicosia A, Colloca S. Efficient immunization of rhesus macaques with an FICV candidate vaccine by heterologous primingboosting with novel adenoviral vectors based on different serotypes. Gene Ther 2006 13 1088-96. 

Various bacterial vectors have been used to express a number of bacterial B. pertussis, S. pneumoniae, Y. pestis, and L. monocytogenes), viral (herpesvirus, influenza virus, human immunodeficiency virus, simian immunodeficiency virus, and hepatitis B virus), and parasitic (5. mansoni, and L. major) antigens. Significant improvements in attenuation of bacteria, and the stability, localization, and expression levels of heterologous antigens are required to market the bacterial vector-based vaccines for use in humans or animals. 

Biodistribution studies are conducted to evaluate the dissemination and persistence of nucleic acid/DNA and viral vector-based vaccines. Vector persistence should be examined at more than one time point up to at least 21 days or more after the last injection 22 unpublished data) and the biodistribution and persistence of a plasmid is usually dependent upon the route of administration.20 These studies can be combined with a general toxicology study or may be conducted separately. In most cases, the DNA is extracted from the selected tissues and assessed by quantitative Polymerase Chain Reaction (qPCR).1516... 

This chapter evaluates some of the approaches used to produce vaccines and heterologous proteins in plants using plant virus-based expression systems, and discusses novel strategies that are being considered for the development of better vectors. 

Inactivated viral particles rgp 120 subunit vaccines rgp 160 subunit vaccines rp 24 subunit vaccines Live vaccines based on viral vectors Octameric V3 peptide Immune Response Genentech/Vaxgen, Biocine, Chiron/Ciba Geigy MicroGenes Sys. Inc., Immuno-Ag. MicroGenes Sys. Inc. Biocine, Merck, Sanofi Pasteur, Targeted Genetics UBI... 

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