[Show abstract][Hide abstract] ABSTRACT: Background: previous studies have demonstrated the superior immunogenicity of high-dose inactivated influenza vaccine (IIV-HD) in older adults compared to standard-dose inactivated influenza vaccine (IIV-SD), as measured by hemagglutination inhibition (HAI) antibody titers against egg-propagated vaccine antigens. The 2012-2013 northern hemisphere influenza season was characterized by high H3N2 activity and by mismatch between predominant circulating strains and egg-propagated vaccines. There is growing interest in evaluating influenza vaccine immune responses beyond the traditional HAI assay.
Methods: samples collected as part of a randomized controlled trial (NCT01427309, sponsored by Sanofi Pasteur) evaluating the efficacy of IIV-HD vs IIV-SD in adults ≥65 years were available for testing; one third of trial participants provided post-vaccination sera. This sub-study utilized a case-cohort design, in which 675 representative samples collected during the 2012-2013 season of the study (from individuals who either developed polymerase chain reaction/culture confirmed H3N2 influenza illness [N=123] or belonged to a random subset of 10% of non-cases [N=552]) were selected for expanded testing. Expanded immunogenicity was assessed with an HAI assay using an MDCK cell-propagated A/Victoria/361 (H3N2) antigen, a viral neutralization assay (NT) using both egg- and cell-propagated A/Victoria/361 (H3N2) antigens, and an enzyme-linked lectin assay (ELLA) for anti-neuraminidase (N2) antibodies. Geometric mean titers (GMT) were estimated for IIV-HD and IIV-SD recipients using weighted averages and were compared as GMT ratios (IIV-HD/IIV-SD).
Results: samples from 318 IIV-HD and 357 IIV-SD recipients were assayed. The GMT ratios (and 95% Confidence Intervals) were 1.48 (1.26; 1.73), 1.53 (1.29; 1.82), 1.75 (1.43; 2.15), and 1.42 (1.23; 1.65) for cell-propagated HAI, egg-propagated NT, cell-propagated NT, and N2-ELLA, respectively. The GMT ratio for the full immunogenicity subset (2879 IIV-HD and 2872 IIV-SD recipients) assessed by HAI assay using egg-propagated A/Victoria/361 was 1.82 (1.71; 1.94).
Conclusion: IIV-HD is associated with significantly improved immunogenicity compared to IIV-SD in older adults as assessed using a range of different assays.
[Show abstract][Hide abstract] ABSTRACT: Persistence of antibodies after a single dose of Tdap vaccine (tetanus, diphtheria, and 5-component acellular pertussis vaccine) was evaluated in a follow-up study of adolescents (N=324) and adults (N=644) who had received Tdap in earlier clinical trials. Outcome measures were seroprotection (tetanus and diphtheria) or seropositivity (pertussis) and geometric mean concentrations. Humoral immune responses to all antigens were robust 1 month after initial immunization, decreased at subsequent measurements, but continued to exceed pre-immunization levels 1, 3, 5, and 10 years later. Protective levels of diphtheria and tetanus antitoxin persisted in 99.3% of adolescents 10 years after a booster dose of Tdap. Seropositivity to 1 or more pertussis antigens also persisted in most adolescents for 10 years. Although tetanus antitoxin responses were similar in adults to those observed in adolescents, diphtheria antitoxin titers were lower, reflecting the fact that a smaller proportion of adults had received diphtheria toxoid in the previous 10 years compared to adolescents. These data will contribute to the selection of the optimal interval for repeat doses of Tdap.