Conjugation of protein antigen to microparticulate β-glucan from Saccharomyces cerevisiae: a new adjuvant for intradermal and oral immunizations

• Published in: Applied microbiology and biotechnology Vol. 80; no. 6; pp. 1053 - 1061
• Main Authors: Berner, Vanessa K, Sura, Michael E, Hunter, Kenneth W. Jr
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01.10.2008; Springer Berlin Heidelberg; Springer
• Subjects: Adjuvant; Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - chemistry; Adjuvants, Immunologic - isolation & purification; Adjuvants, Immunologic - pharmacology; Administration, Oral; Animals; Antibodies - blood; Antigens - administration & dosage; Antigens - chemistry; Antigens - immunology; Applied Microbial and Cell Physiology; beta-Glucans - administration & dosage; beta-Glucans - chemistry; beta-Glucans - isolation & purification; beta-Glucans - pharmacology; Biological and medical sciences; Biotechnology; Carbodiimide; conjugation; Female; Freund's Adjuvant - administration & dosage; Freund's Adjuvant - pharmacology; Fundamental and applied biological sciences. Psychology; Immunization - methods; Immunization, Secondary; Immunoglobulin G - blood; Injections, Intradermal; Life Sciences; Macrophages, Peritoneal - immunology; Mice; Mice, Inbred BALB C; Microbial Genetics and Genomics; Microbiology; Phagocytosis; Saccharomyces cerevisiae - chemistry; Serum Albumin, Bovine - administration & dosage; Serum Albumin, Bovine - chemistry; Serum Albumin, Bovine - immunology; Vaccine; Vaccines, Conjugate - administration & dosage; Vaccines, Conjugate - immunology; β-Glucan; Vaccine; Adjuvant; β-Glucan; Conjugation; Carbodiimide; Ascomycota; Immunization; Yeast; Protein; Fungi; Antigen; Glucan; Conjugation . Carbodiimide; Saccharomyces cerevisiae
• ISSN: 0175-7598; 1432-0614
• DOI: 10.1007/s00253-008-1618-8

Immunostimulatory glucose polymers known as β-glucans have been studied for many years. Our laboratory has prepared and characterized a novel microparticulate β-glucan (MG) from the budding yeast Saccharomyces cerevisiae. Because MG particles are rapidly phagocytized by murine peritoneal macrophages and induce the expression of B7 costimulatory molecules, we hypothesized that MG could serve as a vaccine adjuvant to enhance specific immune responses. Here, we describe a procedure for conjugating the test vaccine antigen bovine serum albumin (BSA) to MG via water-soluble carbodiimide linkage. Conjugates with up to 0.4 mg of BSA/mg MG were prepared. MG/BSA conjugates were still actively phagocytized by mouse peritoneal macrophages. When used to immunize mice by the intradermal route, these conjugates enhanced the primary IgG antibody response to BSA in a manner comparable to the prototypic complete Freund's adjuvant. Although primary oral immunization with MG/BSA caused no increase in serum anti-BSA antibody titers, booster immunization elicited a significant anti-BSA antibody response. These results suggest that protein antigens can be conjugated to MG via a carbodiimide linkage and that these conjugates provide an adjuvant effect for stimulating the antibody response to the protein antigens.