In:
PLOS Medicine, Public Library of Science (PLoS), Vol. 19, No. 5 ( 2022-5-26), p. e1003953-
Abstract:
Heterologous boost vaccination has been proposed as an option to elicit stronger and broader, or longer-lasting immunity. We assessed the safety and immunogenicity of heterologous immunization with a recombinant adenovirus type-5-vectored Coronavirus Disease 2019 (COVID-19) vaccine (Convidecia, hereafter referred to as CV) and a protein-subunit-based COVID-19 vaccine (ZF2001, hereafter referred to as ZF). Methods and findings We conducted a randomized, observer-blinded, placebo-controlled trial, in which healthy adults aged 18 years or older, who have received 1 dose of Convidecia, with no history of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, were recruited in Jiangsu, China. Sixty participants were randomly assigned (2:1) to receive either 1 dose of ZF2001 or placebo control (trivalent inactivated influenza vaccine (TIV)) administered at 28 days after priming, and received the third injection with ZF2001 at 5 months, referred to as CV/ZF/ZF (D0-D28-M5) and CV/ZF (D0-M5) regimen, respectively. Sixty participants were randomly assigned (2:1) to receive either 1 dose of ZF2001 or TIV administered at 56 days after priming, and received the third injection with ZF2001 at 6 months, referred to as CV/ZF/ZF (D0-D56-M6) and CV/ZF (D0-M6) regimen, respectively. Participants and investigators were masked to the vaccine received but not to the boosting interval. Primary endpoints were the geometric mean titer (GMT) of neutralizing antibodies against wild-type SARS-CoV-2 and 7-day solicited adverse reactions. The primary analysis was done in the intention-to-treat population. Between April 7, 2021 and May 6, 2021, 120 eligible participants were randomly assigned to receive ZF2001/ZF2001 ( n = 40) or TIV/ZF2001 ( n = 20) 28 days and 5 months post priming, and receive ZF2001/ZF2001 ( n = 40) or TIV/ZF2001 ( n = 20) 56 days and 6 months post priming. Of them, 7 participants did not receive the third injection with ZF2001. A total of 26 participants (21.7%) reported solicited adverse reactions within 7 days post boost vaccinations, and all the reported adverse reactions were mild, with 13 (32.5%) in CV/ZF/ZF (D0-D28-M5) regimen, 7 (35.0%) in CV/ZF (D0- M5) regimen, 4 (10.0%) in CV/ZF/ZF (D0-D56-M6) regimen, and 2 (10.0%) in CV/ZF (D0-M6) regimen, respectively. At 14 days post first boost, GMTs of neutralizing antibodies in recipients receiving ZF2001 at 28 days and 56 days post priming were 18.7 (95% CI 13.7 to 25.5) and 25.9 (17.0 to 39.3), respectively, with geometric mean ratios of 2.0 (1.2 to 3.5) and 3.4 (1.8 to 6.4) compared to TIV. GMTs at 14 days after second boost of neutralizing antibodies increased to 107.2 (73.7 to 155.8) in CV/ZF/ZF (D0-D28-M5) regimen and 141.2 (83.4 to 238.8) in CV/ZF/ZF (D0-D56-M6) regimen. Two-dose schedules of CV/ZF (D0-M5) and CV/ZF (D0-M6) induced antibody levels comparable with that elicited by 3-dose schedules, with GMTs of 90.5 (45.6, 179.8) and 94.1 (44.0, 200.9), respectively. Study limitations include the absence of vaccine effectiveness in a real-world setting and current lack of immune persistence data. Conclusions Heterologous boosting with ZF2001 following primary vaccination with Convidecia is more immunogenic than a single dose of Convidecia and is not associated with safety concerns. These results support flexibility in cooperating viral vectored and recombinant protein vaccines. Trial registration Study on Heterologous Prime-boost of Recombinant COVID-19 Vaccine (Ad5 Vector) and RBD-based Protein Subunit Vaccine; ClinicalTrial.gov NCT04833101 .
Type of Medium:
Online Resource
ISSN:
1549-1676
DOI:
10.1371/journal.pmed.1003953
DOI:
10.1371/journal.pmed.1003953.g001
DOI:
10.1371/journal.pmed.1003953.g002
DOI:
10.1371/journal.pmed.1003953.g003
DOI:
10.1371/journal.pmed.1003953.g004
DOI:
10.1371/journal.pmed.1003953.g005
DOI:
10.1371/journal.pmed.1003953.t001
DOI:
10.1371/journal.pmed.1003953.t002
DOI:
10.1371/journal.pmed.1003953.s001
DOI:
10.1371/journal.pmed.1003953.s002
DOI:
10.1371/journal.pmed.1003953.s003
DOI:
10.1371/journal.pmed.1003953.s004
DOI:
10.1371/journal.pmed.1003953.s005
DOI:
10.1371/journal.pmed.1003953.s006
DOI:
10.1371/journal.pmed.1003953.s007
DOI:
10.1371/journal.pmed.1003953.s008
DOI:
10.1371/journal.pmed.1003953.s009
DOI:
10.1371/journal.pmed.1003953.s010
DOI:
10.1371/journal.pmed.1003953.s011
DOI:
10.1371/journal.pmed.1003953.s012
DOI:
10.1371/journal.pmed.1003953.r001
DOI:
10.1371/journal.pmed.1003953.r002
DOI:
10.1371/journal.pmed.1003953.r003
DOI:
10.1371/journal.pmed.1003953.r004
DOI:
10.1371/journal.pmed.1003953.r005
DOI:
10.1371/journal.pmed.1003953.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2164823-2
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