[Frontiers in Bioscience S4, 1393-1401, June 1, 2012]

Peptide cross-reactivity: the original sin of vaccines

Darja Kanduc1

1Department of Biochemistry and Molecular Biology, University of Bari, Bari Italy

TABLE OF CONTENTS

1. Abstract
2. Introduction: the "vaccine problem"
3. Antibodies and antigens: cross-reactivity before monoclonal antibodies
4. Antibodies and antigens: cross-reactivity after monoclonal antibodies
5. Cross-reactivity and the molecular mimicry hypothesis
6. Cross-reactivity and the phenomenon of microbial escape from immune surveillance
7. Peptide commonality, immune escape, adjuvanted vaccines and autoimmune cross-reactions. A vicious circle
8. The future of vaccines: the concept of sequence uniqueness
9. References

1. ABSTRACT

Recent studies have demonstrated that an extensive peptide identity platform characterizes entities spanning the entire evolutionary arc from viruses to humans. These studies also established existence of an immune cross-reactivity among viruses and bacteria, as well as between microbial organisms and humans. This peptide commonality presents obstacles to diagnostics, burdens therapeutic vaccinology with harmful collateral effects, and can result in autoimmune diseases. The present study 1) recapitulates the significance of cross-reactivity from the molecular mimicry hypothesis to the phenomenon of microbial immunoevasion; 2) analyzes the implications of cross-reactivity for the self-nonself discrimination issue; 3) highlights the negative role exerted by cross-reactions in translating immunology to effective vaccines; 4) outlines the vicious circle connecting peptide commonality, microbial immune escape, adjuvanted vaccines and autoimmune cross-reactions; and 5) conclusively indicates sequence uniqueness as a basic criterion for designing effective vaccines exempt from autoimmune cross-reactions.