CD8+-T-Cell Response to Secreted and Nonsecreted Antigens Delivered by RecombinantListeria monocytogenesduring Secondary Infection

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Abstract
Understanding how existing antivector immunity impacts live vaccine delivery systems is critical when the same vector system may be used to deliver different antigens. We addressed the impact of antivector immunity, elicited by immunization with attenuatedactA-deficientListeria monocytogenes, on the CD8+-T-cell response to a well-characterized lymphocytic choriomeningitis virus epitope, NP118-126, delivered by infection with recombinantL. monocytogenes. Challenges of immune mice withactA-deficient and with wild-type recombinantL. monocytogenesgenerated similar numbers of CD8+T cells specific for the NP118-126 epitope. High-dose immunization withactA-deficientL. monocytogenesresulted in substantial numbers of CD8+T cells specific for theL. monocytogenesLLO91-99 epitope in the effector and memory stages of the T-cell response. Challenge of these immune mice with recombinantL. monocytogenesresulted in rapid control of the infection and decreased CD8+-T-cell responses against both the secreted and nonsecreted form of the recombinant antigen compared to the response of naïve mice. In contrast, mice immunized with a low dose ofactA-deficientL. monocytogeneshad ∼10-fold fewer effector and memory T cells specific for LLO91-99 and a substantially higher CD8+-T-cell response against the recombinant antigen after challenge with recombinantL. monocytogenes. Although mice immunized with low-doseactA-deficientL. monocytogeneshad a substantial recall response to LLO91-99, which reached the same levels by 5 to 7 days postchallenge as that in high-dose-immunized mice, they exhibited decreased ability to controlL. monocytogenesreplication. Thus, the level of antivector immunity impacts the control of infection and efficiency of priming responses against new antigens introduced with the same vector.