Molecular studies on the diversification of hemagglutinin-specific human neonatal repertoire subsequent to immunization with naked DNA

Vaccine. 2004 Apr 16;22(13-14):1624-30. doi: 10.1016/j.vaccine.2003.10.045.

Abstract

It is well known that newborns and infants respond poorly to immunization with influenza virus vaccines. The poor response of neonates may be related to restricted B cell repertoire and high susceptibility of neonates to high dose tolerance. Protective antibody response against hemagglutinin (HA) of influenza virus is a T-dependent response. While the immunization of neonates with live virus caused a long lasting unresponsiveness, the immunization with a plasmid containing influenza virus HA circumvents the neonatal unresponsiveness. Genetic immunization primes efficiently neonatal HA-specific B cells, and induces memory cell enabling the animals to develop a strong secondary response and to survive to challenge with a lethal dose. The most striking effect of neonatal immunization consists of a shift of neonatal HA-specific B cell repertoire to adult-type as assessed by analysis of reactivity pattern of HA-specific clonotypes. The diversification is associated with the induction of germinal centers, increased number of B220(+)GL-7(+) cells and with the re-expression of RAG genes. This suggests that the receptor revision may contribute to the diversification of HA-specific neonatal B repertoire.

Publication types

  • Review

MeSH terms

  • Animals
  • Animals, Newborn / immunology
  • DNA, Viral / immunology*
  • Hemagglutinin Glycoproteins, Influenza Virus / chemistry*
  • Hemagglutinin Glycoproteins, Influenza Virus / metabolism
  • Humans
  • Immunization
  • Infant, Newborn
  • Influenza Vaccines / immunology*
  • Mice
  • Orthomyxoviridae / genetics
  • Orthomyxoviridae / immunology*
  • Plasmids / immunology
  • Vaccines, DNA / immunology

Substances

  • DNA, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Influenza Vaccines
  • Vaccines, DNA