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Identification of DHBcAg as a potent carrier protein comparable to KLH for augmenting MUC1 antigenicity. | LitMetric

AI Article Synopsis

  • MUC1 is a protein found on the surface of epithelial cancers, and previous studies have shown that combining it with KLH and the adjuvant QS-21 leads to strong antibody responses in cancer patients.
  • The study proposes using Duck Hepatitis B core antigen (DHBcAg) as a more effective and easier-to-work-with alternative to KLH due to its immunogenic properties and ability to be easily purified.
  • Results from mouse experiments showed that while high antibody levels were achieved with both KLH and DHBcAg carriers after vaccinations, switching carriers did not enhance the immune response, indicating that DHBcAg is a strong carrier protein in immunization strategies.

Article 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 25kDa and is easily purified as a single band, but it self aggregates into particles of approximately 6.4x10(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.

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Source
http://dx.doi.org/10.1016/j.vaccine.2005.05.007DOI Listing

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