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Open Access Research article

Presence of antigen-specific somatic allelic mutations and splice variants do not predict for immunological response to genetic vaccination

Jordan T Becker and Douglas G McNeel*

Author Affiliations

Department of Medicine, University of Wisconsin Carbone Cancer Center, 1111 Highland Avenue, Madison, WI 53705, USA

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Journal for ImmunoTherapy of Cancer 2013, 1:2  doi:10.1186/2051-1426-1-2

Published: 29 May 2013

Abstract

Background

Antigen-specific anti-tumor vaccines have demonstrated clinical efficacy, but immunological and clinical responses appear to be patient-dependent. We hypothesized that naturally-occurring differences in amino acid sequence of a host’s target antigen might predict for immunological outcome from genetic vaccination by presentation of epitopes different from the vaccine.

Methods

Using peripheral blood cells from 33 patients who had been treated with a DNA vaccine encoding prostatic acid phosphatase (PAP), we sequenced the exons encoding PAP and PSA genes from somatic DNA to identify single nucleotide polymorphisms. In addition, mRNA was collected to detect alternative splice variants of PAP.

Results

We detected four synonymous coding mutations of PAP among 33 patients; non-synonymous coding mutations were not identified. Alternative splice variants of PAP were detected in 22/27 patients tested. The presence of detectable splice variants was not predictive of immunological outcome from vaccination. Immune responses to peptides encoded by these splice variants were common (16/27) prior to immunization, but not associated with immune responses elicited with vaccination.

Conclusions

These results suggest that antigen-specific immune responses detectable after treatment with this genetic vaccine are specific for the host-encoded antigen and not due to epitope differences between the vaccine and a particular individual’s somatic coding sequence.

Keywords:
PAP; DNA vaccines; Alternative splice variants; Allelic variants