Identification of DHBcAg as a potent carrier protein comparable to KLH for augmenting MUC1 antigenicity Journal Article

Authors: Gathuru, J. K.; Koide, F.; Ragupathi, G.; Adams, J. L.; Kerns, R. T.; Coleman, T. P.; Livingston, P. O.
Article Title: Identification of DHBcAg as a potent carrier protein comparable to KLH for augmenting MUC1 antigenicity
Abstract: MUC1 is expressed at the cell surface of epithelial cancers. We have shown previously that MUC1 conjugated to keyhole limpet hemocyanin (KLH) plus the saponin immunological adjuvant QS-21 induces consistent high titer IgM and IgG antibodies in patients after treatment of their primary or metastatic cancers. KLH however is poorly soluble and heterogeneous making it difficult to work with, and we hypothesize that changing carrier proteins mid-way through a vaccination schedule would further increase antibody titers. Consequently, there is need for an alternative potent carrier protein. Duck Hepatitis B core antigen (DHBcAg) has a molecular weight of approximately 25 kDa and is easily purified as a single band, but it self aggregates into particles of approximately 6.4 × 10 6 Da. Consequently, it is highly immunogenic, easy to work with and amenable to chemical and genetic conjugation to antigens such as MUC1. We compare here in mice the immunogenicity of MUC1 chemically conjugated to KLH or DHBcAg and MUC1-DHBcAg recombinant protein after an initial series of three vaccinations and then after an additional series of three vaccinations with the same or opposite carrier, all mixed with the saponin immunological adjuvant GPI-0100. High titer IgG antibodies were observed in all groups after the initial three vaccinations: MUC1-DHBcAg median ELISA titer 1/51200, RecMUC1-DHBcAg 1/25600 and MUC1-KLH 1/12800. This increased to 1/6553600 after the second set of three immunizations when the carrier remained the same in all three groups, but titers were significantly lower when the carriers were changed for the final three immunizations. These data demonstrate that DHBcAg is an excellent carrier protein and that changing carrier proteins does not further augment immunogenicity. © 2005 Elsevier Ltd. All rights reserved.
Keywords: controlled study; carrier protein; human cell; nonhuman; mouse; metastasis; animal experiment; cancer vaccine; immunogenicity; nucleotide sequence; recombinant protein; mucin 1; hepatitis b virus; molecular weight; immunoglobulin g antibody; antibody titer; keyhole limpet hemocyanin; immunoglobulin m antibody; immunization; cell surface; qs 21; saponin; antigenicity; dhbcag; hepatitis b antigen
Journal Title: Vaccine
Volume: 23
Issue: 39
ISSN: 0264-410X
Publisher: Elsevier Inc.  
Date Published: 2005-01-01
Start Page: 4727
End Page: 4733
Language: English
DOI: 10.1016/j.vaccine.2005.05.007
PROVIDER: scopus
Notes: --- - "Cited By (since 1996): 9" - "Export Date: 24 October 2012" - "CODEN: VACCD" - "Molecular Sequence Numbers: GENBANK: M60677;" - "Source: Scopus"
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MSK Authors
  1. Fusataka Koide
    14 Koide
  2. Govindaswami Ragupathi
    133 Ragupathi