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

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.