Fetal immunization of baboons induces a fetal-specific antibody response

Abstract

Neonates face a high risk of infection because of the immaturity of their immune systems. Although the transplacental transfer of maternal antibodies to the fetus may convey improved postnatal immunity, this transfer occurs late in gestation and may fail to prevent in utero infection. Both fetal immunization and in utero exposure to antigen can result in a state of immunologic tolerance in the neonate. Tolerance induction of fetal and premature infant lymphocytes has become a paradigm for neonatal responsiveness. However, fetal IgM responses have been demonstrated to maternal immunization with tetanus toxoid and to congenital infections such as rubella, toxoplasma, cytomegalovirus and human immunodeficiency virus. Moreover, 1-week-old infants can respond to standard pediatric vaccination, and neonates immunized with polysaccharide antigens do not develop immunologic tolerance. Here, direct immunization of the baboon fetus with recombinant hepatitis B surface antigen produced a specific fetal IgG antibody response. No specific maternal antibody response was detected, eliminating the possibility of vertical antibody transmission to the fetus. Some infants also responded to later vaccinations with hepatitis B surface antigen, indicating that no immunological tolerance was induced by prior fetal immunization. These results characterize the ability of the fetal immune system to respond to in utero vaccination. We demonstrate that active fetal immunization can serve as a safe and efficient vaccination strategy for the fetus and neonate.

Immune reactivity to type VII collagen: implications for gene therapy of recessive dystrophic epidermolysis bullosa

“…33 Recent experiments have shown that the mammalian fetus can develop antibody responses to antigenic stimuli. 34,35 Our observations are compatible with these recent studies, with patient 8 possibly recognizing type VII collagen as a nonself-protein by memory and/or reactive T-cell clones as a result of the suspected in utero exposure to this antigen. The likely in utero sensitization of patient 8 shows the importance of testing all RDEB patients independent of their COL7A1 mutations or type VII collagen expression, before introduction of the exogenous protein during gene or protein therapy.…”

Vaccine responsiveness in premature infants

“…Nevertheless, these responses are impaired when compared with both term and older infants. 5 Thus following vaccination, IgG and IgA Geometric Mean Titres (GMTs) are lower before 12 months of age than after. In addition antibody responses are reduced when vaccine programs are completed early in the 1 st year of life and more rapidly (for example using a 2-3-4 month schedule) compared with programs that finish later and use a longer interval between doses (for example a 2-4-6 schedule).…”

Oral DNA Vaccination In Utero Induces Mucosal Immunity and Immune Memory in the Neonate

“…I nfectious diseases are a major cause of neonatal morbidity and mortality in humans; pathogens involved include HSV, HIV, hepatitis B virus (HBV), 4 group B Streptococcus sp., Hemophilus sp., and Chlamydia sp. (reviewed in Refs.…”