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 3

Antibody kinetics following bivalent mRNA booster vaccination.

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Antibody kinetics following bivalent mRNA booster vaccination. Kinetics ...
Kinetics of plasma (A–O) and saliva (P–U) antibody responses against the SARS-CoV-2 variant Omicron XBB.1.5. Line graphs depict the plasma neutralization responses in the delayed (purple diamonds, n = 24) (A) and immediate (pink triangles, n = 24) (B) arms as previously described in Figure 2, G and H. Line graphs also illustrate the rise and decay of plasma total IgG levels (D and E), total IgA responses (G and H), Fc-γR2a binding (J and K), and antibody-dependent phagocytic activity (M and N), as well as salivary total IgG levels (P and Q) and total IgA (S and T) responses in the delayed (purple diamonds, n = 24) (D, G, J, M, P, and S) and immediate (pink triangles, n = 24) (E, H, K, N, Q, and T) arms, respectively. 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. Modeled decay slopes (C, F, I, L, O, R, and U) describe the half-life and time taken for the respective antibody responses to return to pre-booster baseline levels. Statistical significance was calculated between cohorts using the likelihood ratio test, and where significant, P values are reported (*P ≤ 0.05). Experiments were performed in duplicate.