The potential of anaflatoxin B1 (AnAFB1) conjugated to keyhole limpet hemocyanin (KLH) as a vaccine (AnAFB1-KLH) in controlling the carry over of the aflatoxin B1 (AFB1) metabolite aflatoxin M1 (AFM1) in cow milk is reported. AFB1 is the most carcinogenic compound in food and foodstuffs amongst aflatoxins (AFs). AnAFB1 is AFB1 chemically modified as AFB1-1(O-carboxymethyl) oxime. In comparison to AFB1, AnAFB1 has proven to be non-toxic in vitro to human hepatocarcinoma cells and non mutagenic to Salmonella typhimurium strains. AnAFB1-KLH was used for immunization of cows proving to induce a long lasting titer of anti-AFB1 IgG antibodies (Abs) which were cross reactive with AFB1, AFG1, and AFG2. The elicited anti-AFB1 Abs were able to hinder the secretion of AFM1 into the milk of cows continuously fed with AFB1. Vaccination of lactating animals with conjugated AnAFB1 may represent a solution to the public hazard constituted by milk and cheese contaminated with AFs.
References
[1]
Boutrif E (1995) FAO programmes for prevention, regulation, and control of mycotoxins in food. Nat Toxins 3: 322–326; discussion 341.
[2]
Williams JH, Phillips TD, Jolly PE, Stiles JK, Jolly CM, et al. (2004) Human aflatoxicosis in developing countries: a review of toxicology, exposure, potential health consequences, and interventions. Am J Clin Nutr 80: 1106–1122.
[3]
McLean M, Dutton MF (1995) Cellular interactions and metabolism of aflatoxin: an update. Pharmacol Ther 65: 163–192.
[4]
IARC (1993) Some naturally occurring substances - food items and constituents, heterocyclic aromatic amines and mycotoxins. IARC Monogr Eval Carcinog Risks Hum. Lyon, France: World Health Organization, International Agency for Research on Cancer. pp. 245–391.
[5]
Henry SH, Bosch FX, Troxell TC, Bolger PM (1999) Policy forum: public health. Reducing liver cancer–global control of aflatoxin. Science 286: 2453–2454.
[6]
Bondy GS, Pestka JJ (2000) Immunomodulation by fungal toxins. J Toxicol Environ Health B Crit Rev 3: 109–143.
[7]
Herzallah SM (2009) Determination of aflatoxins in eggs, milk, meat and meat products using HPLC fluorescent and UV detectors. Food Chem 114: 1141–1146.
[8]
U.S. Department of Health and Human Services PHS, National Toxicology Program (2005) Report on Carcinogens, Eleventh Edition.
[9]
Eaton DL, Ramsdell HS, Neal GE (1994) Biotransformation of Aflatoxins. Toxicology of Aflatoxins:Human Health, Veterinary, and Agricultural Significance: Eaton DL and Groopman JD. San Diego: Academic Press, Inc. pp. 45–71.
[10]
Gallo A, Moschini M, Masoero F (2008) Aflatoxin absorption in the gastro-intestinal tract and in the vaginal mucosa in lactating dairy cows. Ital J Anim Sci 7: 53–63.
[11]
Yousef AE, Marth EH (1989) Stability and degradation of aflatoxin M1. In: van Egmond HP, editor. Mycotoxins in Dairy Products. London: Elsevier Applied Science. pp. 127–161.
[12]
FAO (2004) Worldwide regulations for mycotoxins in food and feed in 2003. FAO Food and Nutrition Paper 81: Food and Agriculture Organization of the United Nations.
[13]
CAST (2003) Mycotoxins: Risk in plant, animal and human system. In: Richard JL, Payne GA, editors. Task Force Report No 139. Ames,, Iowa, USA: Council for Agricultural Science and Technology (CAST).
[14]
Piva G, Galvano A, Pierti A, Piva A (1995) Detoxification methods of aflatoxins. A review. Nutr Res 5: 689–715.
[15]
Chu FS, Hsia MT, Sun PS (1977) Preparation and characterization of aflatoxin B1-1-(O-carboxymethyl) oxime. J Assoc Off Anal Chem 60: 791–794.
[16]
Ueno I, Chu FS (1978) Modification of hepatotoxic effects of aflatoxin B1 in rabbits by immunization. Experientia 34: 85–86.
[17]
Odunola OA, Uwaifo AO (1998) Binding reaction of aflatoxin B1 with immunoglobulin G against aflatoxin B1-bovine serum albumin complex. Afr J Med Med Sci 27: 1–4.
[18]
Odunola OA, Uwalfo AO (2000) Immune response to aflatoxin B1-histone H1 complex. Afr J Med Med Sci 29: 105–110.
[19]
European Commission (2001) Commission Regulation 2001/466/EC of 8 March 2001 setting maximum levels for certain contaminants in foodstuffs (Text with EEA relevance). Off J Eur Commun L77: 1–13.
[20]
Diaz DE, Hagler WM Jr, Blackwelder JT, Eve JA, Hopkins BA, et al. (2004) Aflatoxin binders II: reduction of aflatoxin M1 in milk by sequestering agents of cows consuming aflatoxin in feed. Mycopathologia 157: 233–241.
[21]
Masoero F, Gallo A, Moschini M, Piva G, Diaz D (2007) Carryover of aflatoxin from feed to milk in dairy cows with low or high somatic cell counts. Animal 1: 1344–1350.
[22]
Wagter LC, Mallard BA, Wilkie BN, Leslie KE, Boettcher PJ, et al. (2000) A Quantitative Approach to Classifying Holstein Cows Based on Antibody Responsiveness and Its Relationship to Peripartum Mastitis Occurrence. J Dairy Sci 83: 488–498.
[23]
Nino-Soto MI, Heriazon A, Quinton M, Miglior F, Thompson K, et al. (2008) Differential gene expression of high and low immune responder Canadian Holstein dairy cows. Dev Biol (Basel) 132: 315–320.
[24]
Hernandez A, Karrow N, Mallard BA (2003) Evaluation of immune responses of cattle as a means to identify high or low responders and use of a human microarray to differentiate gene expression. Genet Sel Evol 35: S67–81.
[25]
Newman MJ, Truax RE, French DD, Dietrich MA, Franke D, et al. (1996) Evidence for genetic control of vaccine-induced antibody responses in cattle. Vet Immunol Immunopathol 50: 43–54.
[26]
Lambrecht BN, Kool M, Willart MA, Hammad H (2009) Mechanism of action of clinically approved adjuvants. Curr Opin Immunol 21: 23–29.
[27]
Xu Q-H, Zhao X-N, Cheng J-P, Wei C-H, Zhang Q-H, et al. (2006) Influence of Carrier Proteins on the Immunologic Response to Haptenic Antitetrodotoxin Vaccine. Bioconjugate Chem 17: 1508–1513.
[28]
Kutz RE, Sampson JD, Pompeu LB, Ledoux DR, Spain JN, et al. (2009) Efficacy of Solis, NovasilPlus, and MTB-100 to reduce aflatoxin M1 levels in milk of early to mid lactation dairy cows fed aflatoxin B1. J Dairy Sci 92: 3959–3963.
[29]
Diaz D, Hagler W, Hopkins B, Whitlow L (2003) Aflatoxin Binders I: In vitro binding assay for aflatoxin B1 by several potential sequestering agents. Mycopathologia 156: 223–226.
[30]
European Community (1986) 1986/609/EC. Council Directive 86/609/EEC of 24 November 1986 on the approximation of laws, regulations and administrative provisions of the Member States regarding the protection of animals used for experimental and other scientific purposes. Official Journal L 358: 1–28.
[31]
Nociari M, Shalev A, Benias P, Russo C (1998) A novel one-step, highly sensitive fluorometric assay to evaluate cell-mediated cytotoxicity. J Immunol Methods 213: 157–167.
[32]
Maron DM, Ames BN (1983) Revised methods for the Salmonella mutagenicity test. Mutat Res 113: 173–215.
[33]
Wong JJ, Hsieh DP (1976) Mutagenicity of aflatoxins related to their metabolism and carcinogenic potential. Proc Natl Acad Sci U S A 73: 2241–2244.
[34]
Lee N, McAdam D, Skerritt J (1995) Hapten synthesis and development of ELISAs for detection of endosulfan in water and soil. J Agric Food Chem 43: 1730–1739.
[35]
National Research Council (2001) Nutrient requirements of dairy cattle, seventh revised edition. National Academy of Science, Washington, D.C.
[36]
European Commission (2002) Commission Regulation 2002/1226/EC of 8 July 2002 amending annexes A and B of the consolidated Council Directive 64/432/EEC. Off J Euro Commun L179: 13–18.
[37]
AOAC (1995) Preparation of standards for mycotoxins. In: Helrich KC, editor. Official methods of analysis of the AOAC. Arlington, USA: Association of Official Analytical Chemists (AOAC).
[38]
Littell RC, Henry PR, Ammerman CB (1998) Statistical analysis of repeated measures data using SAS procedures. J Anim Sci 76: 1216–1231.
