Kollmann Tobias R, Reikie Brian, Blimkie Darren, Way Sing Sing, Hajjar Adeline M, Arispe Kiea, Shaulov Angela, Wilson Christopher B
Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195, USA.
J Immunol. 2007 Mar 15;178(6):3695-701. doi: 10.4049/jimmunol.178.6.3695.
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.
新生儿极易受到感染,并且对大多数常用疫苗的反应也欠佳。然而,如果将抗原引入抗原呈递细胞(APC)的细胞质中,新生儿体内可以引发CD8 T细胞反应。单核细胞增生李斯特菌(Lm)靶向APC的细胞质,在成年小鼠中是一种强大的促进CD8和CD4 Th1的疫苗载体。我们假设,即使在新生儿中,减毒的Lm菌株也将是安全的,并能诱导持久的保护性免疫。我们发现,仅用减毒株DeltaactA-Lm免疫一次的新生小鼠就产生了强大的初次和二次CD8和CD4 Th1反应,并且在无需加强免疫的情况下,完全受到了强毒野生型Lm致死攻击的保护。此外,表达异源重组抗原的DeltaactA-Lm诱导了针对该抗原的强烈CD8和Th1记忆反应。基于这些数据,我们提出DeltaactA-Lm或其衍生物可能作为新生儿免疫的疫苗载体。