Most existing vaccines do not induce protective immunity immediately following birth, nor do they retain protective efficacy in the latter years of life without booster doses. Using a mouse model, we present evidence that a live-replicating vaccine administered only once shortly after birth was able to induce both immediate and lifelong protection. Newborn mice immunized with a safe, highly attenuated strain of Listeria monocytogenes (Lm) were already protected by day 7 post-vaccination when challenged with a virulent strain of Lm. Furthermore, all mice remained fully protected for 2 years after only a single immunization. Vaccine-specific T cell immune responses were still detectable 2 years later, indicating long-lived immune memory even in neonatal vaccine recipients. Analysis of memory precursor subsets, specific for antigens homologous to Lm or a model vaccine (Ova), demonstrated remarkable similarity between adult and neonatal vaccine recipient effector and central memory CD8 T cell development. The magnitude of expansion of antigen specific memory T cells post-infectious challenge correlated with protection in both groups. This is the first direct evidence that vaccination--even in the absence of a booster dose--is capable of inducing immediate and lifelong protective immune memory regardless of age at the time of initial vaccination.
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