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Randomized Controlled Trial
. 2025 Mar 22;15(1):9882.
doi: 10.1038/s41598-025-92742-x.

SARS-Cov-2 vaccination strategies in hospitalized recovered COVID-19 patients: a randomized clinical trial (VATICO Trial)

Sofía Sábato #  1   2 , Susana Benet #  1   2 , Angela J Rogers  3 , Thomas A Murray  4 , Melissa Skeans  4 , Beatriz Mothe  1   2   5   6   7 , Roger Paredes  1   2   5 , Ahmad Mourad  8 , Francis Kiweewa  9   10 , Dena Kamel  11 , Mamta K Jain  11 , Joseph Lutaakome  12 , Mary Grace Nalubega  9 , Nicholus Sebudde  9   10 , Eleftherios Mylonakis  13 , Dominique L Braun  14 , Timothy Hatlen  15 , Ivan Kimuli  16 , Cissy Kitko  17 , Henry Mugerwa  17 , Jonathan Kitonsa  12 , Kami Kim  18 , Phyllis C Tien  19 , Jeroen Highbarger  20 , Ashley L McCormack  21 , Adriana Sanchez  22 , Daniel D Murray  23 , Abdel G Babiker  24 , Victoria J Davey  25 , D Clark Files  26 , Annetine C Gelijns  27 , Elizabeth S Higgs  28 , Virginia L Kan  29 , Gail V Matthews  30 , Sarah L Pett  24 , H Clifford Lane  31 , Cavan Reilly  4 , Anna L Goodman  24   32 , Jens D Lundgren #  23 , José Moltó #  33   34   35 ; ACTIV-3/VATICO study group and the STRIVE Network
Collaborators, Affiliations
Randomized Controlled Trial

SARS-Cov-2 vaccination strategies in hospitalized recovered COVID-19 patients: a randomized clinical trial (VATICO Trial)

Sofía Sábato et al. Sci Rep. .

Abstract

The impact on immunogenicity and efficacy of SARS-CoV-2 vaccination in people with prior COVID-19 could differ depending on timing of vaccination and number of doses. The VATICO study randomized 66 hospitalized recovered COVID-19 individuals to receive either immediate or deferred vaccination, with one or two doses of mRNA SARS-CoV-2 vaccines. We measured binding and neutralizing antibodies against SARS-CoV-2 at enrollment and longitudinally. Median (IQR) time from SARS-CoV-2 infection to first vaccination was 68 (53-75) days in the immediate group, and 151 (137-173) days in the deferred group. At week 48, timing or number of vaccine doses did not influence the change in antibody levels relative to baseline. Adherence to the assigned vaccine regimen was lower in the deferred group, particularly in participants receiving two doses. Although the study ultimately lacked adequate power to draw firm conclusions, these results suggest possible benefits of prompt vaccination after recovery from COVID-19.

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Conflict of interest statement

Declarations. Competing interests: B.M., reports consultancy, advisory and/or speaker fees from AELIX Therapeutics, Gilead Sciences, AbbVie, Janssen, ViiV and MSD. R.P., has served on advisory boards for Gilead Sciences Inc., Pfizer Inc., Roche Therapeutics, MSD, GSK, ViiV Healthcare, Eli Lilly and Company, Astra Zeneca, Exevir, PharmaMar and Atea Pharmaceuticals Inc. He has had research grants paid to his institution by MSD, ViiV Healthcare, Gilead Sciences, and PharmaMar. M.K.J., has received research funding directed to her institution from Gilead Sciences, AbbVie, and Laurent. D.L.B., received money for advisory boards, lectures and travel grants paid to himself from the companies Gilead, MSD, ViiV and Pfizer. K.K., has received research funding from NIH, Astra Zeneca, Pfizer, Abbott, Romark, MSD, and Novartis and has served on advisory boards for the Burroughs Wellcome Fund, ParaFRAP, and the Sanford Guide. P.C.T., has received a grant support from Merck which was paid to her institution. G.V.M., have served on advisory board for Astra Zeneca. A.G., is named as an inventor on a patent covering a promoter construct used in ChAdOx1-vectored vaccines, including ChAdOx1 nCoV-19 vaccine, and has received royalty income through the University of Oxford’s from sales of Astra Zeneca vaccines and its sublicensees under the University’s revenue sharing policy whith potential benefits in the future. AG has also collaborated with Moderna and Novavax through her organization on commercial vaccine projects, which provided funding directly to the trials and the organization but not to her personally. J.M., has received research funding, consultancy fees and lecture sponsorships from and have served on advisory boards for MSD, Gilead Sciences, ViiV Healthcare, and Johnson & Johnson. The other authors declare non-financial competing interests.

Figures

Fig. 1
Fig. 1
Study design. (A) Timeline from participation in TICO to enrollment in VATICO. (B) Diagram of study visits. TICO IMP: TICO Investigational Medical Product (Tixagevimab/Cilgavimab and Ensovibep or Placebo).
Fig. 2
Fig. 2
Consolidated Standards of Reporting Trials (CONSORT) flow diagram for the trial. *Out of window of ± 7 days of the per-protocol scheduled visit.
Fig. 3
Fig. 3
Anti-S IgG antibody levels in plasma during the study (means and 95% confidence intervals). (A) Immediate (blue) vs. deferred (red) vaccination. (B) One-dose (red) vs. two-dose (blue). The vertical grey dashed lines indicate the timing of vaccine administration for each group.
Fig. 4
Fig. 4
Effect and 95% confidence interval for vaccination timing on anti-S IgG Ab levels at week 48 reported overall and by subgroup as a geometric mean ratio (GMR) comparing immediate versus deferred vaccination. An effect > 1 indicates a higher 48-week antibody level with immediate vaccination. Effect estimates reflect adjustments for anti-S IgG Ab levels at baseline and the other factorial randomization, i.e. one-dose versus two-dose vaccination. TICO randomization group ACTIVE: NMAb (Tixagevimab/Cilgavimab or Enzovibep). TICO symptom duration: days from COVID symptoms onset to TICO enrollment.
Fig. 5
Fig. 5
Effect and 95% confidence interval for number of vaccination doses on anti-S IgG Ab levels at week 48 reported overall and by subgroup as a geometric mean ratio (GMR) comparing one versus two doses. An effect > 1 indicates higher 48-week antibody level with one dose than with two doses. Effect estimates reflect adjustments for anti-S IgG Ab levels at baseline and the other factorial randomization, i.e. immediate versus deferred vaccination. TICO randomization group ACTIVE: NMAb (Tixagevimab/Cilgavimab or Enzovibep). TICO symptom duration: days from COVID symptoms onset to TICO enrollment.
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