Effect of age on serum immunoglobulin G subclass antibody responses to inactivated influenza virus vaccine.

We previously reported an age-associated impairment of serum immunoglobulin G (IgG) antibody responses to inactivated influenza virus vaccine. The present study extends these observations by examining the IgG subclass distribution of vaccine responses measured by enzyme linked immunosorbent assay in healthy adults aged < 40 (young), 40-64 (middle-aged), and > or = 65 (elderly) years. Serological responses in all age groups showed antibodies that were predominantly IgG1 and secondarily IgG3. Influenza antigen-specific IgG4 titers did not change following vaccination, and antibodies of the IgG2 subclass were not detected in any serum specimens. Aging was associated with a significant impairment of IgG1, but not of IgG3, antibody production. Relative differences in the magnitude and frequency of response between IgG1 and IgG3 subclasses, which were present in young and middle-aged adults (viz., IgG1 > IgG3), were less apparent in the elderly. This observation was confirmed in a second analysis of IgG subclass-specific responses in a separate cohort of elderly vaccinees. These results suggest that the age-related impairment of humoral responses to inactivated influenza virus vaccine is primarily accounted for by differences in IgG1 antibody production, and that IgG3 antibodies make up a larger proportion of the overall serologic response in the elderly than they do in younger persons.