Induction of protective immunity to Listeria monocytogenes in neonates.
Neonates suffer unduly from infections and also respond suboptimally to most commonly used vaccines. However, a CD8 T cell response can be elicited in neonates if the Ag is introduced into the cytoplasm of APCs. Listeria monocytogenes (Lm) targets the cytoplasm of APC and is a strong CD8 and CD4 Th1-promoting vaccine vehicle in adult mice. We hypothesized that an attenuated strain of Lm would be safe and induce long-lasting protective immunity, even in neonates. We found that neonatal mice immunized only once with the attenuated strain DeltaactA-Lm developed robust primary and secondary CD8 and CD4 Th1 responses and were fully protected from lethal challenge with virulent wild-type Lm without the need for a booster immunization. Furthermore, DeltaactA-Lm expressing a heterologous recombinant Ag induced a strong CD8 and Th1 memory response to that Ag. Based on these data, we propose that DeltaactA-Lm or derivatives thereof might serve as a vaccine vehicle for neonatal immunization.
Kollmann
Tobias R
TR
Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195, USA. tkollmann@cw.bc.ca
Reikie
Brian
B
Blimkie
Darren
D
Way
Sing Sing
SS
Hajjar
Adeline M
AM
Arispe
Kiea
K
Shaulov
Angela
A
Wilson
Christopher B
CB
D000818:Animals; D000831:Animals, Newborn; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000382:microbiology; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D001428:Bacterial Vaccines / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology* / Q000517:prevention & control; D008565:Membrane Proteins / Q000172:deficiency / Q000276:immunology; D051379:Mice; D018417:Th1 Cells / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology / Q000494:pharmacology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D008565:Membrane Proteins; D014613:Vaccines, Attenuated; C072980:actA protein, Listeria monocytogenes