Epstein-Barr virus but not cytomegalovirus is associated with reduced vaccine antibody responses in Gambian infants

Abstract

Background: Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are persistent herpesviruses that have various immunomodulatory effects on their hosts. Both viruses are usually acquired in infancy in Sub-Saharan Africa, a region where childhood vaccines are less effective than in high income settings. To establish whether there is an association between these two observations, we tested the hypothesis that infection with one or both viruses modulate antibody responses to the T-cell independent meningococcal polysaccharide vaccine and the T-cell dependent measles vaccines.

Methodology/principal findings: Infection with EBV and CMV was diagnosed by the presence of virus-specific IgM in the peripheral blood or by the presence of IgG at higher levels than that found in umbilical cord blood. Anti-meningococcus IgG and IgM were quantified by ELISA. Anti-measles antibody responses were quantified by haemagglutinin antibody inhibition assay. Infants infected with EBV had reduced IgG and IgM antibody responses to meningococcal polysaccharides and to measles vaccine. Infection with CMV alone predicted no changes in the response to meningococcal polysaccharide. While CMV alone had no discernable effect on the antibody response to measles, the response of infants infected with both CMV and EBV was similar to that of infants infected with neither, suggesting that the effects of CMV infection countered the effects of EBV on measles antibody responses.

Conclusions: The results of this exploratory study indicate that infection with EBV is associated with reduced antibody responses to polysaccharides and to measles vaccine, but suggest that the response to T-cell dependent antigens such as measles haemagglutinin may be restored by infection with CMV.

Figure 1. Study Design.

A Study design showing times at which samples were collected, EBV and CMV serology was carried out, vaccines were administered and vaccine-specific responses were measured. B numbers of infants in the cohort and involved in analysis, and numbers infected with EBV and CMV at nine and eleven months.

Figure 2. Infection with EBV but not CMV downregulates antibody responses to measles.

Infection with EBV is associated with reduced antibody responses to measles unless infants are coinfected with CMV. Plots of serum haemagglutinin-inhibiting activity at eleven months of age, plotted against the serostatus at A the time of vaccination at nine months of age and B the time of sampling at eleven months of age. Titres are expressed as log₂. Grey bars indicate medians. Significances refer to the statistical interaction between the effects of EBV and CMV infection.