Vaccines formulations

It was also shown that, unlike CFA and many other adjuvants, Adjuvax itself is nonantigenic (data not shown) allowing repeated use of Adjuvax-based drug or vaccine formulations with minimal side-effects. In addition, unlike many other oil or detergent based adjuvants, the saline based Adjuvax does not cause local... 

Singleantigen vaccine formulations should be administered in a 2-dose schedule at either 0 and 6-12 months (Havrix ), or 0 and 6-18 months (Vaqta ). If the rombined hepatitis A and hepatitis B vaccine (Twinrix ) is used, administer 3 doses at 0,1, and 6 months. 

Although the lipospheres seem to fit very well in vaccine formulations provided by injection or by oral intake, apparently not much has been published in this field since our last review [12], This chapter is an update of the that review, with an emphasis on the possible use of lipospheres for oral immunization. 

The neutral fats used in the preparation of the hydrophobic core of the several liposphere-vaccine formulations described here included tricaprin and tristearin, stearic acid, and ethyl stearate. The phospholipids used to form the surrounding layer of lipospheres were egg phosphatidylcholine and dimyristoyl phosphatidylg-lycerol. Polymeric biodegradable lipospheres were prepared from low molecular weight polylactide (PLA) and polycaprolactone-diol (PCL). 

No antibody activity was found after oral immunization in any of the individual rabbits immunized with liposphere R32NS 1-vaccine formulation. However, rabbit immunization by all parenteral routes tested resulted in enhanced immunogenicity, with increased antibody IgG levels over the entire postimmunization period. The individual rabbit immune response shows that immunization by subcutaneous injection was the most effective vaccination route among all parenteral routes of administration tested. 

The effect of alum as adjuvant was also tested in the liposphere-vaccine formulation. In the presence of lipid A, enhanced immune response is obtained even in the absence of alum. This observation is very important because there is increasing concern about the toxic side effects of alum in the long term. Research has suggested a link between aluminum and diseases of the brain, including Alzheimer s disease. 

Olive, C., Schulze, K., Sun, H. K., Ebensen, T., Horvath, A., Toth, I., and Guzman, C. A. (2007). Enhanced protection against Streptococcus pyogenes infection by intranasal vaccination with a dual antigen component M protein/Sfbl lipid core peptide vaccine formulation. Vaccine 25, 1789-1797. 

A vaccine formulation contains antigenic components that are obtained from or derived from the pathogen. These pathogens include mainly viruses, bacteria, parasites, and fungi. Research has shown that the part of the pathogen that causes disease, termed virulence, can be decoupled from the protective part, so-called immunity. Vaccine development focuses on means to reduce the virulence factor while retaining the immunity stimulation. Administration... 

In order to study in vitro the activation potential of the vaccine formulation, 4x10 BmDCs were incubated either with 400 pg free TRP-2 or 40 pg TRP-2 in liposomal formulations. In addition, CpG-ODNs were added in this series of experiments concomitantly either in its free form (20 nmol) or in its liposomal form (5.2 nmol). The incubation took place in 4mL RPMI (with 5% PCS) for 48 hours at 37°C. After completion of the incubation, the cells were stained with antibodies specific for CD80, CD86 and MHC II molecules, which are expressed in high amounts on the surface of DCs after activation. 

Jason Kindrachuk is a postdoctoral fellow at the University of British Columbia (UBC) in the laboratory of Professor R. E. W. Hancock. Jason received his Ph.D. from the University of Saskatchewan in 2007 where his research focused on host and pathogen sensory systems. During his study he specially focused on TLR-9 receptor—ligand interactions and the interactions between host defense peptides and the PhoPQ two-component sensory system of Salmonella typhimurium. In 2008 Jason received the Canadian Cystic Fibrosis Foundation Kin Canada Fellowship for his research in the area of alternative therapies for treatment of antibiotic- and multidrug-resistant bacteria. Currently his research is focused on the investigation of structure-activity relationships amongst natural and synthetic host defense peptides from the perspective of associated immunomodulatory activities and as well as vaccine formulation strategies. 

When new vaccines are developed, new pharmaceutical delivery systems and additives with properties suitable for this new class of vaccines must be developed. Promising additives and delivery systems have to be evaluated regarding their efficacy and toxicity. These vaccine formulations do not simply act as carriers but are also used to enhance the immune response against the administered antigen (as an... 

Kersten, G.E, and D.I Crommelin, Liposomes and ISCOMS as vaccine formulations. Biochim Biophys Acta, 1995. 1241(2) 117-38. 

Another vaccine, formulated by mixing irradiated cells from colon carcinoma cell lines with Detox was injected to patients with colorectal metastatic adenocarcinoma, with or without IL-la [212], The vaccine induced local toxicity, and fatigue which was increased in the group treated with IL-la. DTH occurred in both groups. No clinical response was available. 

The following sections will detail each component within a vaccine formulation and describe its use, source, and limitations. 

Another new adjuvant used in a flu vaccine in Europe is called as MF59, which is a submicron oil in water emulsion containing squalene as the oil phase. This adjuvant emulsion is safe and nontoxic for use in humans and has been tested in several million subjects (13-16). The vaccine formulation contains MF59 (FLUAD) , which is a licensed product in Europe and has been shown to be safe and well tolerated in patients over the last seven years. 

Liposomes are phospholipid vesicles that have been evaluated both as adjuvants and as vehicles for antigens and adjuvants (17). A liposomal hepatitis A (Hep A) vaccine (virosomes) has been extensively evaluated in the clinic and is currently licensed for a Hep A vaccine (18). Alternative adjuvants that have been used in a few products include L-tyrosine (allergy vaccine) and MPL (cancer treatment). The various adjuvants (mainly alum salts) used in vaccine formulations and their quantities per dose are listed in Table 1. 

Another important component of most vaccine formulations is a suitable preservative. The three most commonly used preservatives in available vaccines are phenol, 2-phenoxyethanol, and ethyl mercurithiosalicylate (thimerosal). Thimerosal, in particular, is used in multidose vials as an antimicrobial preservative. Concerns about the presence of mercury in thimerosal (25 pg/dose) has led to FDA stopping the use of this preservative in all vaccines by an amendment to the FDA Modernization Act of 1997. By 2001, thimerosal was removed from most childhood vaccines as a precautionary measure. The sources of all of the preservatives for vaccines are the same suppliers that supply preservatives for the parenteral dosage forms (J. T. Baker, Aldrich, Spectrum, etc. from U.S.A.). Table 2 lists some of the preservative concentrations in common vaccines. 

Table 1 A Representative List of Adjuvants Used in Commercial Vaccine Formulations...

The most commonly used salts in vaccine formulations are sodium chloride, sodium phosphate, succinic acid, and sodium borate. The concentrations of the salts used in any given formulation are based on isotonicity, pH, and other stabilizers being used in the formulations. A typical range is from 5 to 20 mM salt concentration. These concentrations are also selected to reduce pain on injection and to accord rapid normalization with physiological fluid. Surfactants used in MF59 emulsion include Tween 80 and sorbitan trioleate. 

EXCIPIENTS USED IN VACCINE FORMULATIONS CURRENTLY IN CLINICAL TRIALS... 

Several novel vaccine formulations are currently in clinical trials. Some of these will eventually end up as products in the future. Several new polymers are being... 

ANALYTICAL ASSAYS AND QUALITY CONTROL OF EXCIPIENTS FOR VACCINE FORMULATIONS... 

Harrison, G.B., Shakes, T.R., Robinson, C.M., Lawrence, S.B., Heath, D.D., Dempster, R.P., Lightowlers, M.W. and Rickard, M.D. (1999) Duration of immunity, efficacy and safety in sheep of a recombinant Taenia ovis vaccine formulated with saponin or selected adjuvants. Veterinary Immunology and Immunopathology 70, 1 61 -1 72. 

The vaccine formulation comprises a mixture of the outer-membrane lipopolysaccharides from bacteria of the seven different serotypes. The lipopolysaccharides may be obtained from cultures of each of the seven types by the standard procedure of Westphal (11), involving phenol—water extraction of the cells. However, for large-scale purposes, the older procedure of Boivin, (12) involving extraction of the cells with trichloroacetic acid, was... 

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