Spectroscopic characterization of antibodies adsorbed to aluminium adjuvants: correlation with antibody vaccine immunogenicity

Article Article scientifique Article Spectroscopic characterization of antibodies adsorbed to aluminium adjuvants: correlation with antibody vaccine immunogenicity eng 2005-02 author Capelle Martinus 134630 author Brügger Peter author Arvinte Tudor 134040 1686-1694 10.1016/j.vaccine.2004.09.031 15705473 0264-410X MMA383 is an anti-idiotypic antibody designed as an immunogenic surrogate for the cancer specific Lewis Y antigen. Lewis Y is expressed in 70–90% of tumours of epithelial origin with limited expression in normal tissue. Five different MMA383 vaccines were prepared by mixing a MMA383 antibody solution with an Alhydrogel™ aluminium hydroxide adjuvant and tested on the biological activity in a rat model. The immunogenicity increased when: (i) the adjuvant was sterilized at 121 °C compared to no sterilization, (ii) the adjuvant was suspended in a phosphate buffer compared to water and (iii) the MMA383 solution was at a pH of 7.2. The immunogenicity of a ready-to-use MMA383 aluminium hydroxide suspension was the lowest. The in vivo data show that small differences in vaccine formulations before injection can generate significant changes in immunogenicity. Prior to mixing with the adjuvant, the physical and chemical characteristics of MMA383 antibodies were the same in all vaccines. Fluorescence and light scattering methods were developed to characterize antibodies in the presence of the adjuvant. Compared to the least active vaccines, the two most biologically active vaccines showed an increase in the antibody Trp fluorescence intensity, anisotropy, fluorescence lifetime, 90° light-scatter, sedimentation velocity and rotational correlation time. Analysis of the 90° light-scatter sedimentation kinetics indicates that stronger immune responses of vaccines can be related to the stronger binding of the antibodies to the adjuvants and the formation of more compact and condensed particles. Taken together, these results show a correlation between the in vitro fluorescence and light-scatter data and the in vivo immune response of the five MMA383 vaccines. The spectroscopic techniques described offer a new in vitro approach for the prediction of immune responses of different vaccine formulations. Monoclonal antibody Adjuvant Immune response Fluorescence spectroscopy Light-scatter Dewey 615 31 Section des sciences pharmaceutiques 17 false Vaccine 23 14 49e02007-9d87-4c82-9293-96a77b3761c9 Article (Published version) Restricted Martinus_VAC_2005231686.pdf 254661 application/pdf 46703f5d84eddb4638a788a30b6544ea2e1b4f646efcc34e7b93e800dc8db45b restrictedAccess Faculté des sciences / Section des sciences pharmaceutiques

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Spectroscopic characterization of antibodies adsorbed to aluminium adjuvants: correlation with antibody vaccine immunogenicity	Vaccine			2005	47	0

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Capelle, Martinus