CD8(+)-T-cell response to secreted and nonsecreted antigens delivered by recombinant Listeria monocytogenes during secondary infection.
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 attenuated actA-deficient Listeria monocytogenes, on the CD8(+)-T-cell response to a well-characterized lymphocytic choriomeningitis virus epitope, NP118-126, delivered by infection with recombinant L. monocytogenes. Challenges of immune mice with actA-deficient and with wild-type recombinant L. monocytogenes generated similar numbers of CD8(+) T cells specific for the NP118-126 epitope. High-dose immunization with actA-deficient L. monocytogenes resulted in substantial numbers of CD8(+) T cells specific for the L. monocytogenes LLO91-99 epitope in the effector and memory stages of the T-cell response. Challenge of these immune mice with recombinant L. monocytogenes resulted 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 of actA-deficient L. monocytogenes had approximately 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 recombinant L. monocytogenes. Although mice immunized with low-dose actA-deficient L. monocytogenes had 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 control L. monocytogenes replication. Thus, the level of antivector immunity impacts the control of infection and efficiency of priming responses against new antigens introduced with the same vector.
Tvinnereim
Amy R
AR
Department of Microbiology, Interdisciplinary Graduate Program in Immunology, The University of Iowa, Iowa City, Iowa 52242, USA.
Hamilton
Sara E
SE
Harty
John T
JT
D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology; D007700:Kinetics; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009698:Nucleoproteins / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D014611:Vaccination; D014774:Virulence
D000942:Antigens, Bacterial; D000956:Antigens, Viral; D001426:Bacterial Proteins; D018984:Epitopes, T-Lymphocyte; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009698:Nucleoproteins; D010446:Peptide Fragments; D052899:Pore Forming Cytotoxic Proteins; D011993:Recombinant Fusion Proteins; C094246:nucleoprotein peptide 118-126, lymphocytic choriomeningitis virus; D054353:Perforin; C072980:actA protein, Listeria monocytogenes