Inhibition of Vaccine Responses by Maternal Antibodies

Abstract

The inhibition of seroconversion by maternal antibodies after vaccination is a widely observed phenomenon in human and veterinary medicine. One of the best documented examples of this type of antibody interference is measles vaccination. Using the cotton rat (Sigmodon hispidus) model of measles virus pathogenesis, we have determined that maternal antibodies use a mechanism designed to prevent an overshooting immune (B cell) response. Maternal antibodies suppress B cell responses through crosslinking of the B-cell receptor (BCR) with FcγIIB receptor (CD32). CD32 is not expressed on T cells, and this explains why B cells are preferentially suppressed by maternal antibodies whereas T cell responses are usually detectable after vaccination. B cells can be stimulated through cross-linking of the BCR to the complement receptor 2 (CR2) via a complex of IgM, vaccine and C3d complement protein. During a successful primary immunization, children develop IgG as well as IgM antibodies, and this explains why they generate a B cell response after a second immunization in spite of IgG levels which would be inhibitory in children with maternal antibodies. For vaccine development, it is of importance to note that stimulation of B cell responses in the presence of maternal antibodies through type I interferon is successful because it activates two receptors (interferon receptor and CD21) on the B cell surface. These findings indicate that, for immunization in the presence of maternal antibodies, adjuvants should be used which stimulate type I interferon. In the presence of maternal antibodies, children can be immunized with vaccines which stimulate a protective T cell response. The only clinical solution to stimulating a protective B cell response in the presence of maternal antibodies is to immunize children repeatedly. © 2013 by Pediatric Infectious Diseases Society.