It has been contended that limited data exist on sex-difference in immune response with
vaccines in humans. However, a comprehensive search of the literature retrieved 97 studies with 14
vaccines influenza (7 studies),
hepatitis A (15 studies),
hepatitis B (50 studies), pnuemococcal polysaccaride (4 studies),
diphtheria (4 studies),
rubella (3 studies),
measles (2 studies),
yellow fever (3 studies), meningococcal A (1 study), meningococcal C (1 study),
tetanus (1 study), brucella (1 study),
Venezuelan equine encephalitis (1 study) and
rabies (4 studies), with sex-difference in humoral (antibody) response. These differences are associated with sex-difference in the clinical efficacy of
influenza,
hepatitis A,
hepatitis B, pneumococcal
polysaccharide and
diphtheria vaccines and significant adverse reactions with
rubella,
measles and
yellow fever vaccines. The genesis of these differences is uncertain but not entirely related to
gonadal hormones (differences are seen in pre-pubertal and post-menopausal subjects not on
hormone replacement therapy) or female sex (males had greater serological response for pneumococcal,
diphtheria,
yellow fever,
Venezuelan equine encephalitis and in some studies with
rabies vaccine. As sex-difference in humoral immune response was seen with most
vaccines which cover the spectrum of mechanisms by which infectious agents cause disease (mucosal replication, viral viraemia, bacterial bacteraemia, toxin production and neuronal invasion), it is mandatory that
vaccine trialists recruit a representative sample of females and males to be able to assess sex-differences which may have clinical implications.