Protective Cellular Immunity Against Influenza VirusInduced by Plasmid Inoculation of Newborn Mice

Abstract

Neonate organisms display an intrinsic disability to mount effective immune responses to infectious agents or conventional vaccines. Whereas low. doses of antigens trigger a suboptimal response, higher doses are frequently associated with tolerance induction. We investigated the ability of a plasmid-expressing nucleoprotein of influenza virus to prime a specific cellular immune response when administered to newborn mice. We found that persistent exposure to antigen following plasmid inoculation of neonates leads to a vigorous priming of specific CTLs rather than tolerance induction. The CTLs were cross-reactive against multiple strains of type A influenza viruses and produced IFNγ but no IL-4. The immunity triggered by plasmid inoculation of neonates was protective in terms of pulmonary virus clearance as well as survival rate following lethal challenge with influenza virus. Whereas the persistence of the plasmid at the site of injection was readily demonstrable in adult mice at 3 months after inoculation, mice immunized as newborns displayed no plasmid at 3 months and very little at 1 month after injection. Thus, DNA-based immunization of neonates may prove an effective and safe vaccination strategy for induction of cellular immunity against microbes that cause serious infectious diseases in the early period of life.

Plasmid Vaccination with Insulin B Chain Prevents Autoimmune Diabetes in Nonobese Diabetic Mice

“…Thus, coadministration of IL-4 is not merely shifting the profile from T1 to T2 but has a more profound impact on the overall peripheral repertoire, consistent with an effect on APC (27). Because neonatal inoculation of plasmid is associated with substantially shorter persistence of transgene (34), the prolongation of vaccination schedule may optimize exposure of emerging self-reactive T cells to InsB chain in circumstances when the intrinsic disease kinetics is slower, as in the case of male NOD mice.…”

Update on Antiviral DNA Vaccine Research (1998–2000)

“…Consistent with this concern, a DNA vaccine encoding the circumsporozoite protein of malaria induced tolerance in neonates [131]. However, DNA vaccines coding for viral proteins mounted effective immune responses in newborn mice, which was in contrast to vaccination with UV-inactivated virus strains [132,133]. Moreover, DNA vaccination was only slightly affected by the dam's immune status and also provided effective immune induction in aged mice [134].…”

Perinatal Activation of the Interleukin-33 Pathway Promotes Type 2 Immunity in the Developing Lung

“…cord blood, it was proposed that delayed postnatal maturation of Th cell function and developmental defects within the innate immune system that result from feto-maternal adaptation predisposes young children to Th2 cell sensitization (Bot et al, 1998 Results are shown as mean ± SEM. *p < 0.05, **p < 0.01.…”