Purpose: This study uses a high-throughput glycan microarray to profile anti-glycan immune responses to whole-cell vaccines: GVAX Pancreas, K562-GM and H1299. The aim was to indentify anti-glycan antibody responses relevent to patient clinical outcomes Results: Immune responses to non-human antigens bovine fetuin and alpha-Gal antigens were identified induced by GVAX Pancreas. The magnitude of these responses inversely correlate with patient survival. The non-human antigens were likely incorporated from cell media used for vaccine production. Their presence distracted immune system, resulting in decreased immune response to vaccine antigens. Conclusion: This study highlighted the importance of anti-glycan immune response in vaccine development. Whole-cell vaccinesderived from human cell lines could incorporate non-human antigens from cell media. These xeno-antigens may have negative impact on the vaccine efficacy.
Overall design
Anti-glycan antibodies in Pre- and Post-vaccination sera from 62 patients treated with GVAX Pancreas (n=28), K562-GM vaccine (n=26) and H1299 vaccine (n=8) were profiled with glycan microarrays. Responses in anti-glycan IgG and IgM antibodies were quantified by calculating the fold-changes to indivudal antigens before and after vaccination. The magnitude of antibody response was used to evaluate the correlation with patient survival. The results from Kaplan-Meier estimate and Cox regression analysis were further validated with permutations.Finally, mechanistic studies were performed to rationalize the observed inverse correlations between anti-glycan immune responses and patient survival.
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