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 4

Breakthrough COVID-19.

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Breakthrough COVID-19. Kaplan-Meier probability of remaining negative fo...
Kaplan-Meier probability of remaining negative for symptomatic COVID-19 during the study in the delayed (purple) and immediate (pink) arms (A). Analysis includes all first on-study COVID-19 symptomatic infections (pre- and post-study vaccination, self-reported). The probability for the delayed arm reaches zero because the final 3 delayed arm participants were positive/censored just after 12 months, whereas there were 5 final immediate arm participants who remained at risk. The numbers below the graph show the remaining number of participants at risk (number censored) during the study at baseline (0 mo), month 3 (3 mo), month 6 (6 mo), month 9 (9 mo), and month 12 (12 mo). Statistical significance between survival curves was calculated by log-rank Mantel-Cox test. Line graphs show the plasma (B–D) and salivary (E–G) antibody responses against Omicron XBB.1.5 from 4 representative individuals (green) with COVID-19 breakthrough infections (rapid antigen test–positive [RAT-positive]). Total IgG (B and E), total IgA responses (C and F), and Fc-γR2a binding (D and G) against Omicron XBB.1.5 are shown following symptom onset. Line graphs also depict the kinetics of N-specific IgG for both the delayed (purple diamonds) (H) and immediate (pink triangles) (I) arms across sampling time points, highlighting individuals with known symptomatic (RAT-positive; green) and asymptomatic (>4-fold rise in N-specific IgG from the previous time point; yellow) breakthrough infections. Experiments were performed in duplicate. (J) Kaplan-Meier plot showing the probability of remaining COVID-19 negative during the study in the delayed (purple) and immediate (pink) arms. Analysis includes all first on-study COVID-19 infections (pre- and post-study vaccination, self-reported, and asymptomatic laboratory diagnosis). The probability for the delayed arm reaches zero because the final 2 delayed arm participants were positive/censored just after 12 months, whereas there were 3 final immediate arm participants who remained at risk (log-rank P = 0.838, by Mantel-Cox test).