Abstract

Immunological memory can be defined as the ability to mount a response of greater magnitude and with faster kinetics upon re-encounter of the same antigen. We have previously reported that a booster dose of a protein antigen given 15 days after the first dose interferes with the development of memory, i.e., with the ability to mount an epitope-specific IgG response of greater magnitude upon re-encounter of the same antigen. We named the time-window during which memory is vulnerable to disruption a “consolidation phase in immunological memory”, by analogy with the memory consolidation processes that occur in the nervous system to stabilize memory traces. In this study, we set out to establish if a similar memory consolidation phase occurs in the IgG response to a B cell epitope displayed on a filamentous bacteriophage. To this end, we have analyzed the time-course of anti-β-amyloid IgG titers in mice immunized with prototype Alzheimer’s Disease vaccine fdAD(2-6), which consists of a fd phage that displays the B epitope AEFRH of β -amyloid at the N-terminus of the Major Capsid Protein. A booster dose of phage fdAD(2-6) given 15 days after priming significantly reduced the ratio between the magnitude of the secondary and primary IgG response to β-amyloid. This analysis confirms, in a phage vaccine, a consolidation phase in immunological memory, occurring two weeks after priming.

Highlights

  • Long-lasting antibody responses and immunological memory are the desired outcomes of vaccination [1,2,3]

  • A consolidation phase in immunological memory is defined operationally as the time window during which a booster dose reduces the subsequent immunological memory, that is the ability to display an enhanced response to a late re-encounter [10]

  • The consolidation phase in immunological memory was first identified in the IgG response to a B cell epitope of β-amyloid displayed on a multimeric protein [10]

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Summary

Introduction

Long-lasting antibody responses and immunological memory are the desired outcomes of vaccination [1,2,3]. We observed a statistically significant decrease in the ratio between the height of the secondary and primary response IgG peaks in a treatment group that had received a booster injection of antigen 15 days after the first dose. Treatment groups that had received the booster injection 7 or 21 days after the first dose displayed no statistically significant “memory” differences from the single-dose group. We interpreted these observations hypothesizing that, when a booster dose is given 15 days after the first dose, it disrupts the development of immunological memory. By analogy with the memory consolidation processes that occur in the nervous system to stabilize memory traces, we named the time window during which the development of immunological memory is vulnerable to a disrupting stimulus “a consolidation phase of immunological memory [10]”

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