Vaccines adjuvants for

For this reason vaccine formulation tends to follow the traditional routes innovative formulations are rare. Aluminium hydroxide, aluminium phosphate and calcium phosphate are still the only registered vaccine adjuvants for humans. Veterinary vaccines have to rely on the same components, however, a few vaccines containing a mineral oil adjuvant (Marcol) or saponin (Quil A or derivatives) have passed the registration hurdles. It remains to be seen whether and under which restrictions these adjuvants can be used in the EEC after 1996 (see also below in "Additional requirements for veterinary products"). 

O Hagan, D.T. Recent advances in vaccine adjuvants for systemic and mucosal administration. J. Pharm. Pharmacol. 1997, 49, 1-10. 

Adjuvants are substances which can modify the immune response of an antigen (139,140). With better understanding of the functions of different arms of the immune system, it is possible to explore the effects of an adjuvant, such that the protective efficacy of a vaccine can be improved. At present, aluminum salt is the only adjuvant approved for use in human vaccines. New adjuvants such as QS-21, 3D-MPL, MF-59, and other liposome preparations are being evaluated. Several of these adjuvants have been in clinical trial, but none have been approved for human use. IL-12 has been proposed as an adjuvant which can specifically promote T-helper 1 ceU response, and can be a very promising adjuvant for future vaccine development. 

Several TLR-4 adjuvants for vaccines have been developed to date. An example of these is monopho-sphoryl lipid A (MJPL) a modified version of lipid A found in LPS [4]. It has been used extensively in clinical trials as it is far less toxic than LPS. It is hoped to use MPL in vaccines against infectious diseases, allergies and cancer. Derivatives of MPL have now been... 

The nasal tissue is highly vascularized and provides efficient systemic absorption. Compared with oral or subcutaneous administration, nasal administration enhances bioavailability and improves safety and efficacy. Chitosan enhances the absorption of proteins and peptide drugs across nasal and intestinal epithelia. Gogev et al. demonstrated that the soluble formulation of glycol chitosan has potential usefulness as an intranasal adjuvant for recombinant viral vector vaccines in cattle [276]. 

The development of vaccines based on S-layer technologies has focused on two strategies (1) exploiting S-layers present on pathogenic organisms, and (2) use of S-layer lattices as carrier/adjuvants for vaccination and immunotherapy [100,101]. 

The primary course of DTP protection consists of three doses of a combined vaccine, each dose separated by at least 1 month and commencing not earlier than 2 months of age. In such combinations the pertussis component ofthe vaccine acts as an additional adjuvant for the toxoid components. Monovalent pertussis and tetanus vaccines, and combined vaccines lacking the pertussis component (DT) are available. If pertussis vaccination is contraindicated or refused then DT vaccine alone should be offered. The primary course of pertussis vaccination is considered sufficient to confer life-long protection, especially since the mortality associated with disease declines markedly after infancy. The risks associated with tetanus and diphtheria infection persist... 

Greenland JR, Letvin NL (2007) Chemical adjuvants for plasmid DNA vaccines. Vaccine 25 3731-3741... 

Few substances have had a greater positive impact upon human healthcare management than antibodies, vaccines and adjuvants. For most of this century, these immunological agents have enjoyed widespread medical application, predominantly for the treatment/prevention of infectious diseases. As a group, they are often referred to as biologies (Chapter 1). 

Saponins are a family of glycosides (sugar derivatives) widely distributed in plants. Each saponin consists of a sugar moiety bound to a sapogenin (either a steroid or a triterpene). The immunostimulatory properties of the saponin fraction isolated from the bark of Quillaja (a tree) has been long recognized. Quil A (which consists of a mixture of related saponins) is used as an adjuvant in selected veterinary vaccines. However, its haemolytic potential precludes its use in human vaccines. Research efforts continue in an attempt to identify individual saponins (or derivatives thereof) that would make safe and effective adjuvants for use in human medicine. 

M. T. De Maqistris. Zonula occludens toxin as a new promising adjuvant for mucosal vaccines. Vaccine 24 S60-S61 (2006). 

Current efforts in vaccine development have predominantly utilized clade B isolates, which represent the subtype in North America and Western Europe. There is also an increased interest in the development of clade A and C vaccines for the expanding pandemic in Asia and sub-Saharan Africa. A concern in fhe clade-specific vaccine strategy is the potential inability to produce large amounts of vaccine specific for distinct clades. This leaves open the question of specific vs. cross-clade effectiveness. Choice of immunogen(s), adjuvant, dose, and mode of administration are also additional variables that must be addressed in candidate vaccine research. 

Very often, vaccines are formulated with certain substances to enhance the immune response. These substances are called adjuvants (from the Latin adju-vare, which means to help ). The most common adjuvants for human use are aluminum hydroxide, aluminum phosphate, and calcium phosphate. Other adjuvants being used include bacteria and cholesterol. Mineral oil emulsions are normally the adjuvants used in animal studies. The adjuvant known as Freund s complete adjuvant consists of killed tubercle bacilli in water-inmineral oil emulsion, and Freund s incomplete adjuvant is a water-in-oil emulsion. Both these adjuvants are effective in stimulating an immune response, but they cause unacceptable side effects in humans (see Table 4.2). 

Gupta, R. Siber, G. (1995). Adjuvants for human vaccines — current status, problems and future prospects. Vaccine 13(14), 1263-1274. 

Thymosin is an immunomodulatory peptide produced by the thymus gland and other cells. Thymosin alfa 1, a 28-amino acid peptide, is one member of the family of thymosins that collectively appear to influence a variety of regulatory and counter-regulatory functions in terms of T-cell maturation and antigen recognition, stimulation of native interferons and cytokines such as interleukin-2, and activity of natural killer cell-mediated cytotoxicity. In some countries it is approved as an adjuvant for influenza vaccine or as a treatment for chronic hepatitis B and, in combination with interferon for hepatitis C. Thymosin alfa 1 has been used with some success to treat children with the severe form of Di-George Syndrome. 

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. 

Ott, G, G.L. Barchfeld, D. Chernoff, R. Radhakrishnan, P. van Hoogevest, and G. Van Nest, MF59. Design and evaluation of a safe and potent adjuvant for human vaccines. Pharm Biotechnol, 1995. 6 277-96. 

A wide variety of materials have been explored for their adjuvant activity, although not all are equally effective or nontoxic, especially in humans. Alum and other aluminum salts were first recognized in 1926 and remain the most effective agents licensed for human use by the FDA, although some French products also use calcium phosphate. However, in recent years it has become evident that new and improved vaccine adjuvants are needed. 

The most potent mucosal adjuvants have been shown to be the toxins derived from Vibrio cholerae or Escherichia coli, which should not be surprising since these organisms invade the body through the GI tract. Obviously too toxic for human use because they are the source of cholera or diarrhoea, heat labile enterotoxins have been tested in mice and shown to be potent adjuvants for orally or nasally administered influenza vaccine. The potency of heat-labile enterotoxin mutants may also be enhanced by formulation into bioadhesive particulate delivery systems, and this is an area under current exploration. 

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