Immune response at birth, long-term immune memory and 2 years follow-up after in-utero anti-HBV DNA immunization

V. M. Fazio, F. Ria, E. Franco, P. Rosati, G. Cannelli, E. Signori, P. Parrella, L. Zaratti, E. Iannace, G. Monego, S. Blogna, D. Fioretti, S. Iurescia, R. Filippetti, M. Rinaldi

Research output: Contribution to journalArticlepeer-review

Abstract

Infections occurring at the end of pregnancy, during birth or by breastfeeding are responsible for the high toll of death among first-week infants. In-utero DNA immunization has demonstrated the effectiveness in inducing specific immunity in newborns. A major contribution to infant immunization would be achieved if a vaccine proved able to be protective as early as at the birth, preventing the typical 'first-week infections'. To establish its potential for use in humans, inutero DNA vaccination efficiency has to be evaluated for short- and long-term safety, protection at delivery, efficacy of boosts in adults and effective window/s for modulation of immune response during pregnancy, in an animal model suitable with human development. Here we show that a single intramuscular in-utero anti-HBV DNA immunization at two-thirds of pig gestation produces, at birth, antibody titers considered protective in humans. The boost of antibody titers in every animal following recall at 4 and 10 months demonstrates the establishment of immune memory. The safety of in-utero fetus manipulation is guaranteed by short-term (no fetus loss, lack of local alterations, at-term spontaneous delivery, breastfeeding) and long-term (2 years) monitoring. Treatment of fetuses closer to delivery results in immune ignorance without induction of tolerance. This result highlights the repercussion of selecting the appropriate time point when this approach is used to deliver therapeutic genes. All these findings illustrate the relevance of naked DNA-based vaccination technology in therapeutic efforts aimed to prevent the high toll of death among first-week infants.

Original languageEnglish
Pages (from-to)544-551
Number of pages8
JournalGene Therapy
Volume11
Issue number6
DOIs
Publication statusPublished - Mar 2004

Keywords

  • DNA vaccine technology
  • In-utero vaccination
  • Infectious diseases
  • Intramuscular injection
  • Neonatal immunity
  • Nonviral vectors

ASJC Scopus subject areas

  • Genetics

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