Assessing neonatal responses to vaccination at the protein and gene level: Ig and more Ig

To better understand immunity against pathogens in early life and improve neonatal vaccination strategies, development of B lymphocytes and immunoglobulin (Ig) gene diversity has been investigated in foals.  We can assess the intrinsic humoral immune system development in the fetus and pre-suckle neonate because the equine placenta does not facilitate Ig transfer to the fetus in utero.  We find that equine fetal B cells express mature and co-stimulatory B cell markers and most Ig heavy chain isotype transcripts.  Ig variable region sequence analysis from fetal, neonatal, foal, and adult samples revealed similar Ig heavy chain gene usage, although Ig sequence diversity differed between life stages.

Given these findings, we investigated the response of neonatal foals to vaccination.  Following vaccination with keyhole limpet hemocyanin (KLH) at 3 and 21 days, a robust KLH-specific antibody response was present at 28 days of life.  A separate group of foals was vaccinated with KLH in the presence of maternal antibodies.  KLH-specific antibodies were present at day 28 in these foals as well, although a 10-fold decrease in antibody concentration was measured in this group.  From the vaccinated foals, KLH-specific B cells were isolated for Ig sequencing.  We observed an increase in Ig sequence diversity at days 35 and 42, which was significantly more diverse than non-selected Ig sequences (p = 0.002).  However, these foal Ig sequences encoded less diversity than adult KLH-specific Ig sequences (p = 0.018). 

Thus, neonatal foals are capable of mounting antigen-specific Ig responses to vaccination.