Sex differences in antibody- and cell-mediated immune response to rubella re-immunisation

Antibody (AMI) and cell-mediated (CMI) immunity to rubella virus (RV) were evaluated in healthy adolescent males (n = 11) and females (n = 28) undergoing routine reimmunisation with RA27/3 strain RV as a component of measles-mumps-rubella (MMR) vaccine. Blood samples were collected just before and at 2, 4 and 10 weeks after MMR. While there were no sex differences before MMR and at week 10 after vaccination, levels of specific IgG determined by whole RV enzyme immunoassay were found to be significantly higher in males at weeks 2 and 4, suggesting brisker onset of recall AMI. Analysis of RV protein-specific IgG by immunoblot assays also revealed that while there were no notable sex differences in the distribution of E1-specific antibodies, more males produced E2-specific antibodies whereas more females produced C-specific antibodies after immunisation. Analysis of CMI with whole inactivated RV and a panel of RV synthetic peptides in lymphocyte proliferation assays revealed a brisker onset of CMI in males which paralleled that observed for AMI. The numbers of RV antigens recognised by males were significantly higher at weeks 2 and 4. Also, mean and median stimulation indices measured at weeks 2 and 4 for certain peptides, including two known to contain overlapping antibody neutralisation domains and T-cell epitopes, E1(213-239) and E1(254-285), were also found to be significantly higher in male subjects. These observations suggest that there are hormonal influences on RV-specific immunity which might result in differential handling of RV and, hence, may partially explain why females are more predisposed to adverse outcomes of rubella infection and immunisation.