The preliminary safety and immunogenicity results of a randomized, double-blind, placebo-controlled Phase I trial for a recombinant two-component subunit SARS-CoV-2 vaccine ReCOV
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (ScreenIT)
Abstract
Background
The ReCOV is a recombinant trimeric two-component SARS-CoV-2 subunit vaccine adjuvanted with BFA03. We report the preliminary safety and immunogenicity results for the ReCOV.
Methods
This first in human, randomized, double-blind, placebo-controlled phase I study, was conducted at 2 study sites in New Zealand. Subjects were stratified into two age cohorts (18-55 years and 56-80 years old) and then randomly assigned in a 4:1 ratio to receive two 0.5 mL intramuscular doses of the ReCOV vaccine (20µg or 40µg, adjuvanted with BFA03 in each) or placebo, 21 days apart. The primary endpoints were incidence of solicited local and systemic adverse events (AEs) and unsolicited AEs after each dose; incidence of serious adverse events (SAEs) up to 30 days after the second dose; changes in clinical laboratory tests from baseline up to 7 days after each dose; and changes in vital signs from baseline up to 30 days after the second dose. The key secondary endpoints for immunogenicity were neutralizing antibody titers against SARS-CoV-2, S1 receptor binding domain (RBD) and N-terminal domain (NTD) IgG titers post-vaccination. The T cell-specific immune response elicited by ReCOV were also evaluated. The trial was registered with ClinicalTrials.gov ( NCT04818801 ).
Findings
One hundred participants (50 for each age group) were randomized. The incidence of solicited local AEs in 20μg ReCOV, 40μg ReCOV, and pooled placebo group among younger adults were 60.0%, 70.0%, and 10.0%, respectively, while among older adults were 55.0%, 84.2%, and 10.0%, respectively. The incidence of solicited systemic AEs in 20μg ReCOV, 40μg ReCOV, and pooled placebo group among younger adults were 60.0%, 60.0%, and 30.0%, respectively, while among older adults were 50.0%, 52.6%, and 50.0%, respectively. All solicited AEs and unsolicited AEs were mild. No vaccination-related SAE, adverse events of special interest, and AE leading to early discontinuation were reported.
ReCOV elicited SARS-CoV-2 neutralizing antibody after the first vaccination, which were increased further after the second vaccination irrespective of dose and age groups. The neutralizing antibody against wild-type SARS-CoV-2 peaked at 14 days post the second vaccination in both 20µg and 40µg ReCOV groups, with GMT of 1643.17 IU/mL and 1289.21 IU/mL among younger adults, and 1122.32 IU/mL and 680.31 IU/mL among older adults, respectively. Similarly, both anti-RBD and anti-NTD specific IgG were elicited after the first vaccination, and peaked at 14 days after the second vaccination. T helper 1 biased cellular responses were observed after ReCOV vaccinations.
Interpretation
Both 20 and 40µg ReCOV showed good safety profiles and elicited strong immune responses in the younger and the older adults. The results of this study support the accelerated development of ReCOV.
Funding
Jiangsu Recbio Technology Co., Ltd.
Article activity feed
-
SciScore for 10.1101/2022.05.11.22274932: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: Prior to initiation of the study, the study protocol, and informed consent form were reviewed and approved by the Independent Ethics Committees (ie, Health and Disability Ethics Committee).
IRB: Prior to initiation of the study, the study protocol, and informed consent form were reviewed and approved by the Independent Ethics Committees (ie, Health and Disability Ethics Committee).Sex as a biological variable not detected. Randomization Study design and subjects: This is a randomized, double-blind, placebo-controlled phase I study, conducted at 2 study sites in New Zealand. Blinding Except from prespecified unblinded individuals, all the other investigator, site staff, sponsor, … SciScore for 10.1101/2022.05.11.22274932: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: Prior to initiation of the study, the study protocol, and informed consent form were reviewed and approved by the Independent Ethics Committees (ie, Health and Disability Ethics Committee).
IRB: Prior to initiation of the study, the study protocol, and informed consent form were reviewed and approved by the Independent Ethics Committees (ie, Health and Disability Ethics Committee).Sex as a biological variable not detected. Randomization Study design and subjects: This is a randomized, double-blind, placebo-controlled phase I study, conducted at 2 study sites in New Zealand. Blinding Except from prespecified unblinded individuals, all the other investigator, site staff, sponsor, laboratory staff, and study subjects were blinded to the treatment allocation. Power Analysis Statistical analysis: As a first in human study, the sample size estimation and power calculation were not pre-specified in the protocol, and the number of proposed subjects was considered sufficient to provide a descriptive summary of the safety and immunogenicity of two different dose levels of ReCOV in two age groups. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Subjects who had history of COVID-19 or confirmed SARS-CoV-2 infection; positive test for COVID-19 at screening by reverse transcriptase polymerase chain reaction, or serological test for SARS-CoV-2 immunoglobulin (Ig)M and/or IgG antibodies; received any prior investigational or approved vaccine against a coronavirus at any time; vaccination of licensed inactivated vaccines within 14 days or licensed live or attenuated vaccines within 30 days prior to enrollment in this study; and pregnant women were excluded. SARS-CoV-2 immunoglobulin (Ig)Msuggested: NoneIgG antibodiessuggested: (Rockland Cat# 00-8800-25, RRID:AB_2610703)We evaluated the immunogenicity elicited by ReCOV vaccine in terms of S-RBD and S-NTD IgG binding antibody titers and neutralizing antibody titers against wild-type SAS-CoV-2. SAS-CoV-2suggested: NoneS-RBD and S-NTD specific IgG binding antibodies in serum were measured using a validated laboratory technique of V-Plex SARS-CoV-2 Panel 1 (IgG) Multiplex ELISA (MSD Cat # MESOK15359U-4) by 360Biolabs. SARS-CoV-2 Panel 1 (IgGsuggested: NoneExperimental Models: Cell Lines Sentences Resources Detection of the SARS-CoV-2 neutralizing antibodies was performed using a validated laboratory technique of SARS-CoV-2 microneutralizing assay (cytopathic effect) by the central laboratory 360Biolabs (Melbourne VIC, Australia), with a wild-type strain SARS-CoV-2 hCoV-19/Australia/VIC01/2020 (GenBank MT007544.1) passaged in Vero E6 cells. Vero E6suggested: RRID:CVCL_XD71)Software and Algorithms Sentences Resources All analyses were conducted using SAS Version 9.4 or higher (SAS Institute). SAS Institutesuggested: (Statistical Analysis System, RRID:SCR_008567)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:This study has few limitations. First, the study design did not contain an unadjuvanted group to measure the impact of BFA03 on the safety and immunogenicity, although the pre-clinical studies detected very limited immune response by ReCOV antigen alone, with around 300-fold lower compared to ReCOV.7 Second, the small sample size of the phase I study might not capture the rare occurred adverse events, the safety profile will need further evaluation in larger studies. Third, the primary analysis was performed till 30 days after the second vaccination, long-term safety and immune persistence need to be further evaluated after data collection of ongoing study follow-up. Last, the study mainly evaluated neutralizing antibodies against wild-type SARS-COV-2, although post-hoc analysis indicated cross-neutralizing activities against the Delta variant. Neutralizing activities against Omicron, was not tested due to unavailability of the assay in the central laboratory yet. Limited neutralizing activity against Omicron induced by primary immunization with all other COVID-19 vaccines in market designed for the wild-type strain, as shown that after the primary two-dose series of the mRNA-1273 vaccine, neutralization titers against Omicron variant were 35.0 times lower than those against D614G variant, indicating an increased risk of severe breakthrough infection,18 also there was a significant reduction in GMT of hACE2 receptor binding inhibition against Omicron variant compared to the a...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04818801 Active, not recruiting Safety, Reactogenicity and Immunogenicity Study of ReCOV NCT05084989 Not yet recruiting Efficacy, Safety, and Immunogenicity Study of the Recombinan… NCT05323435 Not yet recruiting Immunogenicity and Safety Study of Recombinant Two-Component… Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
-
