Oral vaccines

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. 

Viruses are the most common cause of diarrheal illness in the world. A live, oral vaccine is licensed and recommended for use in infants for the prevention of rotavirus infection. 

The main prevention strategies include ensuring a safe water supply and safe food preparation, improving sanitation, and patient education. Several oral vaccines are in development, and two are available in countries outside the United States.22-27 However, these vaccines do not provide protection against all cases of cholera because the immunity maybe overcome by high inocula.2... 

The last reported case of indigenous wild-type poliovirus in the United States was in 1979 subsequent cases were all vaccine-associated. In 1997, a transition period to the inactivated poliovirus vaccine was begun to reduce the risk of vac-cine-associated paralytic poliomyelitis. By January 2000, the oral vaccine was no longer recommended for routine use. Currently, the inactivated poliovirus vaccine is recommended for routine use in the United States. The oral poliovirus vaccine is still widely used in some countries where poliovirus eradication has been more difficult. 

Nayak B, Panda AK, Ray P et al (2009) Formulation, characterization and evaluation of rotavirus encapsulated PLA and PLGA particles for oral vaccination. J Microencapsul 26 154-165... 

The most widely studied therapeutic proteins produced in plants include monoclonal antibodies for passive immunotherapy and antigens for use as oral vaccines [40]. Antibodies against dental caries, rheumatoid arthritis, cholera, E. coli diarrhea, malaria, certain cancers, Norwalk virus, HIV, rhinovirus, influenza, hepatitis B virus and herpes simplex virus have been produced in transgenic plants. However, the anti-Streptococcus mutans secretory antibody for the prevention of dental caries is the only plant-derived antibody currently in Phase II clinical trials [40]. Until recently, most antibodies were expressed in tobacco, potato, alfalfa, soybean, rice and wheat [9], It has been estimated that for every 170 tons of harvested tobacco, 100 tons represents harvested leaves. A single hectare could thus yield 50 kg of secretory IgA [3, 41]. Furthermore, it has been estimated that the cost of antibody production in plants is half that in transgenic animals and 20 times lower than in mammalian cell cul-... 

The conventional rabies vaccine was administered to the nine initially naive subjects seven days after completing the oral vaccination. Three of these volunteers produced neutralizing antibodies against rabies virus, although none of the five control subjects did. This study showed a clear indication that the orally delivered rabies vaccine has potential as an oral booster for the conventional rabies vaccine. 

Two types of trivalent poliovirus vaccines are currently licensed for distribution in the United States an enhanced inactivated vaccine (IPV) and a live attenuated, oral vaccine (OPV). IPV is the recommended vaccine for the primary series and booster dose for children in the United States, whereas OPV is recommended in areas of the world that have circulating poliovirus. 

In the poorer countries of the world, where infectious diseases remain the primary cause of death, expense, inadequate health-care infrastructure, and lack of refrigeration limit the utility of vaccines. In these locations, entry of virtually all of these infectious diseases occurs through the host s mucosal surfaces in the gut, and respiratory and reproductive tracts. In 1992, an assembly of philanthropic organizations, in conjunction with the World Health Organization, set about the task of establishing the Children s Vaccine Initiative, whose focus is to advance the development of new technologies that will make novel oral vaccines accessible and... 

Li, H.Y., Ramalingam, S., and Chye, M.L. (2006). Accumulation of recombinant SARS-CoCV spike protein in plant cytosol and chloroplasts indicate potential for development of plant-derived oral vaccines. Exp. Biol. Med. (Maywood) 231(8) 1346-1352. 

Moravec, T., Schmidt, M.A., Herman, E.M., and Woodford-Thomas, T. (2007). Production of Escherichia coli heat labile toxin (LT) B subunit in soybean seed and analysis of its immunogenicity as an oral vaccine. Vaccine 25(9) 1647-1657. 

Streatfleld, S.J. (2006). Mucosal immunization using recombinant plant-based oral vaccines. Methods 38(2) 150-157. 

This chapter first provides a description of immunity in general and then more specifically, immunity in the mucosal immune system. The immune response of both intestinal and respiratory tracts will be described in detail as these are the two most common portals of targeted vaccine development for mucosal immunity. The chapter will cover the basis of mucosal immunity using plant-based oral vaccines. Strategies for increasing mucosal immunity, such as the use of adjuvants, will also be discussed. Finally, the chapter will cover the precliiucal tests and various cliiucal trials that are taking place with respect to production of human and veterinary therapeutic proteins in plants. 

Tacket, C.O. (2009). Plant-based oral vaccines results of human trials. Curr. Top. Micro. Immunol. 332 103-117. 

Investigates the basis of mucosal immunity using plant-based oral vaccines... 

Live (viral) Polio oral vaccine, yellow fever, measles, rubella, mumps, influenza. 

These are discussed elsewhere but include a recombinant vaccinia virus that expresses rabies virus glycoproteins used for oral vaccination. 

A recent development has been the use of genetically modified plants to produce vaccine components. Examples include common foodstuffs such as tomatoes, bananas, potatoes, and com. The prospects for oral vaccines in bananas especially would appear to be promising since this is a staple food in many tropical countries. Vaccine epitopes have also been produced in the milk of goats, sheep, and cows although these may be difficult to purify, process, and formulate. 

O Hagan, D.T. (1994). Novel Delivery Systems for Oral Vaccines. CRC Press, Boca Raton, FL. 

The specificity of the host defence elicited by killed vaccines has been attributed to the O-antlgenic specificity of the vaccine strain (44, 45). Experience with live oral vaccines in mice (46, 47) and man (48) has convincingly demonstrated that also here the presence of the O-antigenlc polysaccharide chain is an important requisite for a protective host response. 

Van der Lubben, I.M., et al. 2001. Chitosan microparticles for oral vaccination preparation, characterization and preliminary in vivo uptake studies in murine Peyer s patches. Biomaterials 22 687. 

Foster, N., and B.H. Hirst. 2005. Exploiting receptor biology for oral vaccination with biodegradable polymers. Adv Drug Deliv Rev 57 431. 

Intravaginal vaccination with whole cell and cholera toxin B subunit (CTB) oral cholera vaccine provided a greater success rate in providing a mucosal immune response in the female genital tract than an oral vaccination [152]. This study demonstrated that in a single individual, systemic immunity did not directly reflect the local antibody response in the mucosal... 

Chen, H., Torchilin, V., and Langer, R. Lectin-bearing polymerized liposomes as potential oral vaccine carriers. Pharm. Res. 13 1378-1383, 1996. 

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