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Freund's Incomplete Adjuvant

Vaxjo ID 9
Vaccine Adjuvant Name Freund's Incomplete Adjuvant
Alternative Names IFA, Incomplete Freund's Adjuvant
Adjuvant VO ID VO_0000142
Description IFA types of adjuvant products have been, and continue to be, used in veterinary vaccine products. Their continued use is based primarily on potency in vaccines where aluminum and saponin adjuvants-based products have failed. These products are typically composed of light mineral oils and purified emulsifiers, such as Montanide ISA 50, and as such, they do not irritate in an unacceptable manner (Jensen et al., 1998).
Stage of Development Research
Components Each ml contains .85 mL paraffin oil and 0.15 ml mannide monooleate. Freund's incomplete adjuvant lacks the mycobacteria found in Complete Freund’s Adjuvant so it minimizes the side-effects. For this reason, Incomplete Freund’s Adjuvant is used for the boost injections (Sigma Aldrich).
Preparation When FIA or FCA was used, equal volumes of antigen (sometimes also containing an additional adjuvant dissolved or suspended in the saline) and oil were emulsified by homogenization for 2 min at full speed in an MSE blender. The water-in oil character of the emulsion was checked for its non-dispersibility in water. Adjuvants in saline were mixed with equal volumes of antigen (Bomford, 1980).
Dosage Unless otherwise indicated, 5-wk-old NOD mice were injected in the hind footpad or i.p. with 50 µ1 of an emulsion of CFA (containing Mycobacterium strain H37Ra), or IFA (DIFCO, Detroit, MI) in saline. (Qin et al., 1993)
Function When added to Freund's incomplete adjuvant with an antigen (e.g., ovalbumin) and injected into hind-foot pads of guinea pigs, this water-soluble adjuvant increases the amount of precipitating antibodies and induces hypersensitivity to ovalbumin and the biosynthesis of -y2-type precipitating antibodies. The water-soluble material has a stronger adjuvant activity than equal amounts of whole bacteria, cell walls, or waxes D, and seems to be the first well-defined, water-soluble, adjuvant-active fraction isolated from Mycobacteria (Adam et al., 1972).
Safety A concern was the possible long-term effects of FIA on the incidence of cancer, autoimmunity and other diseases. US soldiers who received FIA with the influenza vaccine, and a control group ( 20,000 in each group) were followed for 16–18 years and 35 years. No increase in the incidence of any disease or disease-specific death was observed. Regarding short-term effects, FIA-adjuvanted influenza vaccine caused only 40 severe local reactions (including sterile abscesses) in 1,000,000 vaccinated individuals and was safe (without severe local reactions) in the first trial of tetanus toxoid in FIA, which was carried out in Papua New Guinea. However, the second trial had a 59% incidence of severe local reactions (sterile abscesses and persistent painful granulomas at the injection site). At around the same time, a trial of cholera vaccine in FIA carried out in the Philippines was also associated with a high incidence of severe local reactions in the FIA group. In an attempt to explain the cause of this problem in the second tetanus vaccine trial, but not the first and not the influenza vaccine trial, it was suggested that the release of free fatty acids from mannide monooleate by an impure tetanus antigen might have caused the severe local reactogenicity. More-recent data suggest that high doses of antigen in another water-in-oil adjuvant (Montanide ISA 720) might also predispose to this complication (Miller et al., 2005).
Related Vaccine(s)
(Sigma Aldrich): Freund’s Adjuvant, Incomplete []
Adam et al., 1972: Adam A, Ciorbaru R, Petit JF, Lederer E. Isolation and properties of a macromolecular, water-soluble, immuno-adjuvant fraction from the cell wall of Mycobacterium smegmatis. Proceedings of the National Academy of Sciences of the United States of America. 1972; 69(4); 851-854. [PubMed: 4502937].
Bomford, 1980: Bomford R. The comparative selectivity of adjuvants for humoral and cell-mediated immunity. II. Effect on delayed-type hypersensitivity in the mouse and guinea pig, and cell-mediated immunity to tumour antigens in the mouse of Freund's incomplete and complete adjuvants, alhydrogel, Corynebacterium parvum, Bordetella pertussis, muramyl dipeptide and saponin. Clinical and experimental immunology. 1980; 39(2); 435-441. [PubMed: 6248283].
Gregoriadis et al., 1987: Gregoriadis G, Davis D, Davies A. Liposomes as immunological adjuvants: antigen incorporation studies. Vaccine. 1987; 5(2); 145-151. [PubMed: 3604394].
Jensen et al., 1998: Jensen FC, Savary JR, Diveley JP, Chang JC. Adjuvant activity of incomplete Freund's adjuvant. Advanced drug delivery reviews. 1998; 32(3); 173-186. [PubMed: 10837643].
Miller et al., 2005: Miller LH, Saul A, Mahanty S. Revisiting Freund's incomplete adjuvant for vaccines in the developing world. Trends in parasitology. 2005; 21(9); 412-414. [PubMed: 16043410].
Qin et al., 1993: Qin HY, Sadelain MW, Hitchon C, Lauzon J, Singh B. Complete Freund's adjuvant-induced T cells prevent the development and adoptive transfer of diabetes in nonobese diabetic mice. Journal of immunology (Baltimore, Md. : 1950). 1993; 150(5); 2072-2080. [PubMed: 8436836].