PubMed · 5594799
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B R Scazziga. 1967. [Auto-immune thyroiditis].. https://pubmed.ncbi.nlm.nih.gov/5594799/
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Despite the growing demand for combination vaccines, many challenges have been encountered in developing them. It is difficult to predict the physical compatibility and stability of antigens in combination, because these characteristics are highly dependent on vaccine excipients. Clinical evaluation of potential modifications of efficacy of antigens in combination may be alleviated by use of appropriate animal models. Manufacturing issues, such as batch-release testing, storage of intermediate products, and the shift to preservative-free products, are of particular concern because they have the potential to affect the supply chain. Managing changes in the manufacture of one antigen that is a component of several different combination vaccines is also difficult. However, most potential issues can be resolved through the simplification of regulatory processes and harmonization of requirements, such as the acceptance of comparability protocols and antigen master files. Continued collaboration between industry and authorities is necessary to develop effective means of handling all submissions pertaining to combination vaccines.
Combination vaccines differ from single-component vaccines in composition and in how they are manufactured, which poses significant challenges to implementing effective quality-control tests, including measurement of potency. Because each combination vaccine is unique, existing guidelines often fail to provide sufficient information to overcome the inevitable problems encountered when developing and implementing potency tests. Success depends on careful consideration of scientific and regulatory issues. Significant problems may occur if potential interactions between different components in the vaccine are not taken into account during product and test development. Thorough analysis of critical assay parameters and attention to scientific and statistical justifications for the test increase the likelihood of its acceptance. Practical approaches based on experience include rational design of validation studies, complete evaluation and documentation of the potency tests under the conditions in which they are to be applied, and establishing the relationship between production lots of vaccine and lots used in clinical trials.
The proper loading of exogenous peptide antigens affects the transport and cell surface expression of MHC class II molecules. In the present study, the goal was to determine to what extent this step determines the cell surface expression level of MHC class II molecules, such as the HLA-DR. EBV-transformed B-cells, were cultured either in a serum- and protein-free medium, or in a medium that contained different concentrations of exogenous antigens. Using HLA-DR-specific antibodies, the induction of the MHC class II expression was observed in cells that were cultured under serum-and protein-free conditions, when compared to those cultured with exogenous protein antigens. This upregulation was completely suppressed to the normal level by the addition of a high concentration of hen egg lysozyme to the serum- and protein-free medium. This indicates that exogenous proteins regulate the HLA-DR expression. To further examine whether this modulation is controlled at the transcription level, the expression of the HLA-DR beta-chain mRNA was analyzed by reverse transcription-PCR and Northern blots. The same levels of HLA-DRB mRNA were detectable in both culture conditions, indicating that the present observation is dependent on some regulatory mechanisms at the post-transcriptional level. This might include a different pathway for trafficking of HLA-DR molecules to the cell surface, since peptide-binding assays revealed that a high proportion of cell surface HLA-DR molecules under the serum- and protein-free condition were transported to the cell surface without associated peptide antigens.