Although a number of studies have investigated and quantified immune correlates of protection against influenza in adults and children, data on immune protection in the elderly are sparse. A recent vaccine efficacy trial comparing standard-dose with high-dose inactivated influenza vaccine in persons 65 years of age and older provided the opportunity to examine the relationship between values of three immunologic assays and protection against community-acquired A/H3N2 influenza illness. The high-dose vaccine induced significantly higher antibody titers than the standard-dose vaccine for all assays. For the hemagglutination inhibition assay, a titer of 40 was found to correspond with 50% protection when the assay virus was antigenically well matched to the circulating virus—the same titer as is generally recognized for 50% protection in younger adults. A dramatically higher titer was required for 50% protection when the assay virus was a poor match to the circulating virus. With the well-matched virus, some protection was seen at the lowest titers; with the poorly matched virus, high levels of protection were not achieved even at the highest titers. Strong associations were also seen between virus neutralization test titers and protection, but reliable estimates for 50% protection were not obtained. An association was seen between titers of an enzyme-linked lectin assay for antineuraminidase N2 antibodies and protection; in particular, the proportion of treatment effect explained by assay titer in models that included both this assay and one of the other assays was consistently higher than in models that included either assay alone. (This study has been registered at ClinicalTrials.gov under registration no. NCT01427309.)
At 7 years of age, PT children had lower antibody titers to many vaccine antigens than FT children. However, most PT children maintained antibody titers in the protective range.
Antibody avidity to Haemophilus influenzae type b (Hib) polysaccharide (PS) was assessed in infants vaccinated with diphtheria-tetanus-acellular pertussis (DTaP) combined with Hib-PS conjugated to tetanus toxoid (PRP-T) and hepatitis B (HB) (DTaP-PRP-T-HB) and after a PRP-conjugate (CRM197-OS) booster 3-7 months later. Avidity differed between infants with anti-Hib-PS IgG antibody <1 or >1 microg/mL postprimary series (avidity index [AI], 42%, 95% confidence interval [CI], 35%-49%, and 68% and 63%-72%, respectively; P<.0001). For infants with <1 microgram/mL anti-Hib-PS IgG antibody, mean AI rose by the time of preboost immunization to 61% (95% CI, 57%-65%), even though total IgG antibody levels fell. Spontaneous Hib-PS antibody rises after primary series DTaP-PRP-T-HB vaccination were followed by high postboost anti-Hib-PS IgG antibody levels and avidity. The DTaP-PRP-T-HB combination vaccine studied elicits high avidity antibody, and affinity maturation appears to occur in the absence of further antigen exposure even in those with very low anti-Hib-PS antibody.
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