The oral immunogenicity of BioProtein, a bacterial single-cell protein, is affected by its particulate nature

The bacterial single-cell protein BioProtein (BP; Norferm Danmark, Odense, Denmark), produced by fermentation of natural gas with methanotrophic bacteria, is a potential protein source for man and animals. For human consumption, removal of the nucleic acid is necessary. Preliminary studies have shown that ingested BP induces a specific immune response. The objective of the present study was to characterize the type of response, its development over time and product-related causative factors. Mice were fed with diets containing 60 g nucleic acid-reduced BP/kg, 240 g nucleic acid-reduced BP/kg, 240 g untreated BP (basic BP)/kg or 240 g casein/kg (control). In another study, mice were fed 240 g basic BP/kg, whole cell-free BP-culture homogenate or control diet. The immune response was monitored using an ELISA for BP-specific immunoglobulin in blood and BP-specific immunoglobulin A in blood and saliva. Ingested BP induced a steady specific mucosal and systemic immune response, characterized by a dose-dependent production of immunoglobulin and immunoglobulin A in blood and immunoglobulin A in saliva. Basic BP and nucleic acid-reduced BP induced identical responses. However, feeding mice BP-culture homogenate induced immunoglobulin A in saliva but there was no systemic response. The antibodies from BP-fed mice cross-reacted with BP-culture homogenate revealing the presence of the same antigenic components in the two products despite the different oral immunogenicity. Thus, ingestion of BP induces a persistent mucosal and systemic immune response of which the systemic response can be avoided by ingesting a BP preparation free of whole cells. This indicates the importance of the non-particulate constitution of single-cell protein products intended for human or animal consumption.

[1]  Bali Pulendran,et al.  Lipopolysaccharides from Distinct Pathogens Induce Different Classes of Immune Responses In Vivo1 , 2001, The Journal of Immunology.

[2]  T Ahmed,et al.  Immune response to food antigens: Kinetics of food‐specific antibodies in the normal population , 1997, Acta paediatrica Japonica : Overseas edition.

[3]  M. Kerr,et al.  CHAPTER 2 – PROPERTIES OF IMMUNOGLOBULINS , 1994 .

[4]  H. Schägger,et al.  Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis for the separation of proteins in the range from 1 to 100 kDa. , 1987, Analytical biochemistry.

[5]  H. Flad,et al.  Components of gut bacteria as immunomodulators. , 1998, International journal of food microbiology.

[6]  A. Dannaeus Age‐related antibody response to food antigens , 1993, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.

[7]  S. Strobel,et al.  Immune responses to dietary antigens: oral tolerance. , 1998, Immunology today.

[8]  P. Johnson,et al.  Human serum antibodies reactive with dietary proteins. IgG subclass distribution. , 1988, International archives of allergy and applied immunology.

[9]  P. Artursson,et al.  Microparticles as potentially orally active immunological adjuvants. , 1989, Vaccine.

[10]  U. Dahlgren,et al.  Expression of a dietary protein in E. coli renders it strongly antigenic to gut lymphoid tissue. , 1991, Immunology.

[11]  R. Finn,et al.  Human Serum Antibodies Reactive with Dietary Proteins , 1988 .

[12]  J. Mcghee,et al.  A T cell/B cell/epithelial cell internet for mucosal inflammation and immunity , 2004, Springer Seminars in Immunopathology.

[13]  P. Brandtzaeg,et al.  Development and basic mechanisms of human gut immunity. , 2009, Nutrition reviews.

[14]  C. Dolman Oral Immunization , 1945, The American journal of the medical sciences.

[15]  M. Poulsen,et al.  Immunotoxicity of nucleic acid reduced BioProtein--a bacterial derived single cell protein--in Wistar rats. , 2002, Toxicology.

[16]  R. C. Kuhad,et al.  Microorganisms as an alternative source of protein. , 2009, Nutrition reviews.

[17]  R. Coombs,et al.  Naturally developing antibodies to wheat gliadin fractions and to other cereal antigens in rabbits, rats and guinea pigs on normal laboratory diets. , 1983, International archives of allergy and applied immunology.

[18]  V. Barkholt,et al.  Amino acid analysis: determination of cysteine plus half-cystine in proteins after hydrochloric acid hydrolysis with a disulfide compound as additive. , 1989, Analytical biochemistry.

[19]  T. Kita,et al.  Oral immunization with size-purified microsphere beads as a vehicle selectively induces systemic tolerance and sensitization. , 2000, Vaccine.

[20]  Y. Ikada,et al.  Size effect on systemic and mucosal immune responses induced by oral administration of biodegradable microspheres. , 1996, Vaccine.

[21]  R. Medzhitov,et al.  Innate immune recognition: mechanisms and pathways , 2000, Immunological reviews.

[22]  J. Jensenius,et al.  Humoral immunity to dietary antigens in healthy adults. Occurrence, isotype and IgG subclass distribution of serum antibodies to protein antigens. , 1985, International archives of allergy and applied immunology.

[23]  U. Dahlgren,et al.  Difference between bacterial and food antigens in mucosal immunogenicity , 1989, Infection and immunity.

[24]  S. Hachimura,et al.  Serum antibody response elicited by a casein diet is directed to only limited determinants of alpha s1-casein. , 1993, International archives of allergy and immunology.

[25]  Anupama,et al.  Value-added food: single cell protein. , 2000, Biotechnology advances.

[26]  N. Scrimshaw,et al.  Nutritional Value and Safety of “Single Cell Protein” , 2001 .

[27]  M. Moeremans,et al.  Sensitive colloidal metal (gold or silver) staining of protein blots on nitrocellulose membranes. , 1985, Analytical biochemistry.

[28]  S. Davis,et al.  Microparticulate absorption from the rat intestine , 1994 .

[29]  Ermak,et al.  Microparticle targeting to M cells. , 1998, Advanced drug delivery reviews.

[30]  H. Kleivdal,et al.  Outer membrane proteins of Methylococcus capsulatus (Bath) , 1997, Archives of Microbiology.

[31]  Y. Tabata,et al.  Rectal immunization with antigen-containing microspheres induces stronger Th2 responses than oral immunization: a new method for vaccination. , 2001, Vaccine.

[32]  M. Añón,et al.  Detection and characterization of antibodies specific to food antigens (gliadin, ovalbumin and beta-lactoglobulin) in human serum, saliva, colostrum and milk. , 1998, Clinical and experimental immunology.

[33]  J. Goding 2 – The Antibody Response , 1996 .

[34]  Fossati,et al.  Detection and characterization of antibodies specific to food antigens (gliadin, ovalbumin and β‐lactoglobulin) in human serum, saliva, colostrum and milk , 1998 .

[35]  K. McCoy,et al.  IgA responses in the intestinal mucosa against pathogenic and non-pathogenic microorganisms. , 2001, Microbes and infection.

[36]  H. Weiner,et al.  Suppression of experimental autoimmune encephalomyelitis by oral administration of myelin basic protein. III. Synergistic effect of lipopolysaccharide. , 1990 .

[37]  C. Whitacre,et al.  Suppression of experimental autoimmune encephalomyelitis by the oral administration of myelin basic protein. , 1988, Cellular immunology.