Preliminary Findings From the Dynamics of the Immune Responses to Repeat Influenza Vaccination Exposures (DRIVE I) Study: A Randomized Controlled Trial

Abstract

Background: Studies have reported that repeated annual vaccination may influence influenza vaccination effectiveness in the current season.

Methods: We established a 5-year randomized placebo-controlled trial of repeated influenza vaccination (Flublok; Sanofi Pasteur) in adults 18-45 years of age. In the first 2 years, participants were randomized to receive vaccine or saline placebo as follows: placebo-placebo (P-P), placebo-vaccine (P-V), or vaccine-vaccine (V-V). Serum samples were collected each year just before vaccination and after 30 and 182 days. A subset of serum samples collected at 5 time points from 95 participants were tested for antibodies against vaccine strains.

Results: From 23 October 2020 through 11 March 2021 we enrolled and randomized 447 adults. Among vaccinated individuals, antibody titers increased between days 0 and 30 against each of the vaccine strains, with smaller increases for repeat vaccinees who on average had higher prevaccination titers in year 2. There were statistically significant differences in the proportions of participants achieving ≥4-fold rises in antibody titer for the repeat vaccinees for influenza A(H1N1), B/Victoria, and B/Yamagata, but not for A(H3N2). Among participants who received vaccination in year 2, there were no significant differences between the P-V and V-V groups in geometric mean titers at day 30 or the proportions of participants with antibody titers ≥40 at day 30 for any of the vaccine strains.

Conclusions: In the first 2 years, during which influenza did not circulate, repeat and first-time vaccinees had similar postvaccination geometric mean titers to all 4 vaccine strains, indicative of similar levels of clinical protection. Clinical Trials Registration. NCT04576377.

Keywords: ELISA; antibody; immunogenicity; influenza; vaccination.

Figure 1.

Study flow chart showing participant enrollment into the study; randomization into placebo-placebo (P-P), placebo-vaccine (P-V), and vaccine-vaccine (V-V) groups; interventions received; and follow-up. The random samples were selected from participants who provided serum samples at these 5 time points: year 1, days 0, 30, and 182, and year 2, days 0 and 30.

Figure 2.

Antibody titers at various time points measured by hemagglutination inhibition (HAI) assay for influenza A(H1N1) and B, and by focus reduction neutralization test (FRNT₉₀) for influenza A(H3N2). Measured titers are plotted for each group 0, 30, and 182 days after vaccination in year 1 and 0 and 30 days after vaccination in year 2, and lines represent geometric mean titers at each time point.

Figure 3.

Antibody titers at various time points measured by enzyme-linked immunosorbent assay for influenza A(H1N1) and A(H3N2). Measured titers are plotted at 0 and 30 days after vaccination in years 1 and 2, and lines represent geometric mean antibody titers at each time point.