Randomized controlled trial reveals no benefit to a 3-month delay in COVID-19 mRNA booster vaccine
Wen Shi Lee, … , Kevin J. Selva, Stephen J. Kent
Wen Shi Lee, … , Kevin J. Selva, Stephen J. Kent
Published July 11, 2024
Citation Information: J Clin Invest. 2024;134(17):e181244. https://doi.org/10.1172/JCI181244.
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Clinical Research and Public Health

Randomized controlled trial reveals no benefit to a 3-month delay in COVID-19 mRNA booster vaccine

Abstract

BACKGROUND There is uncertainty about the timing of booster vaccination against COVID-19 in highly vaccinated populations during the present endemic phase of COVID-19. Studies focused on primary vaccination have previously suggested improved immunity with a longer interval between the first and second vaccine doses.METHODS We conducted a randomized, controlled trial (November 2022–August 2023) and assigned 52 fully vaccinated adults to an immediate or a 3-month delayed bivalent Spikevax mRNA booster vaccine. Follow-up visits were completed for 48 participants (n = 24 per arm), with collection of saliva and plasma samples following each visit.RESULTS The rise in neutralizing antibody responses to ancestral and Omicron strains were almost identical between the immediate and delayed vaccination arms. Analyses of plasma and salivary antibody responses (IgG, IgA), plasma antibody-dependent phagocytic activity, and the decay kinetics of antibody responses were similar between the 2 arms. Symptomatic and asymptomatic SARS-CoV-2 infections occurred in 49% (21 of 49) participants over the median 11.5 months of follow-up and were also similar between the 2 arms.CONCLUSIONS Our data suggest that there was no benefit in delaying COVID-19 mRNA booster vaccination in preimmune populations during the present endemic phase of COVID-19.TRIAL REGISTRATION Australian New Zealand Clinical Trials Registry number 12622000411741 (https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12622000411741).FUNDING National Health and Medical Research Council, Australia (program grant App1149990) and Medical Research Future Fund (App2005544).

Authors

Wen Shi Lee, Jennifer Audsley, Mai-Chi Trieu, Arnold Reynaldi, L. Carissa Aurelia, Palak H. Mehta, Joanne Patterson, Helen E. Kent, Julie Nguyen, Thakshila Amarasena, Robyn Esterbauer, Ebene R. Haycroft, Pradhipa Ramanathan, Miles P. Davenport, Timothy E. Schlub, Joseph Sasadeusz, Adam K. Wheatley, Amy W. Chung, Jennifer A. Juno, Kevin J. Selva, Stephen J. Kent

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Figure 2

Neutralizing antibodies following bivalent mRNA booster vaccination.

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Neutralizing antibodies following bivalent mRNA booster vaccination. Pla...
Plasma neutralizing activity was measured using a live virus neutralization assay against SARS-CoV-2 Omicron BA.1 (A–E) and XBB.1.5 (F–J) variants. Pre-booster (A and F) and post-booster day-14 (D14) (D and I) and day-84 (D84) (E and J) neutralizing antibody responses were compared between the delayed (blue/purple diamonds, n = 24) and immediate arms (pink triangles, n = 24) at the respective sampling time points. Line graphs describe the kinetics of plasma neutralization activity of the delayed (B and G) and immediate (C and H) arms after receiving the bivalent booster. Numbers above each time point describe the respective median neutralization IC50 against each viral variant. Dotted lines depict the detection threshold for the assay (neutralization IC50 = 20). Dark purple diamonds and lines show the antibody responses of the 3 individuals who received the BA.5 bivalent booster in the delayed arm of the study. Saliva neutralizing activity against ancestral SARS-CoV-2 was measured using the sVNT (Genscript). Pre-booster (K) and post-booster day-14 (N) neutralizing antibody responses were compared between the delayed (purple diamonds, n = 18) and immediate arms (pink triangles, n = 19), respectively. Line graphs describe the change in saliva neutralization activity following the bivalent booster (L and M). Numbers describe the percentage of surrogate neutralization observed at each time point. Dotted lines depict the sVNT cutoff for neutralizing activity (30%). Statistical significance was calculated between cohorts and time points using the 2-tailed Mann-Whitney U test or the Kruskal-Wallis test followed by Dunn’s multiple-comparison test. Paired saliva analysis (day 0 vs. day 14) was performed using the Wilcoxon matched-pairs, signed-rank test. Experiments were performed in duplicate. Graphs are displayed as the median, and where significant, P values are reported (**P ≤ 0.01, ***P ≤ 0.001, and ****P ≤ 0.0001).