Aerosolized Ad5-nCoV booster vaccination elicited potent immune response against the SARS-CoV-2 Omicron variant after inactivated COVID-19 vaccine priming

This article has been Reviewed by the following groups

Read the full article See related articles

Abstract

The SARS-CoV-2 Omicron variant has become the dominant SARS-CoV-2 variant around the world and exhibits immune escape to current COVID-19 vaccines to some extent due to its numerous spike mutations. Here, we evaluated the immune responses to booster vaccination with intramuscular adenovirus-vectored vaccine (Ad5-nCoV), aerosolized Ad5-nCoV, a recombinant protein subunit vaccine (ZF2001) or homologous inactivated vaccine (CoronaVac) in those who received two doses of inactivated COVID-19 vaccines 6 months prior. We found that the Ad5-nCoV booster induced potent neutralizing activity against the wild-type virus and Omicron variant, while aerosolized Ad5-nCoV generated the greatest neutralizing antibody responses against the Omicron variant at day 28 after booster vaccination, at 14.1-fold that of CoronaVac, 5.6-fold that of ZF2001 and 2.0-fold that of intramuscular Ad5-nCoV. Similarly, the aerosolized Ad5-nCoV booster produced the greatest IFNγ T-cell response at day 14 after booster vaccination. The IFNγ T-cell response to aerosolized Ad5-nCoV was 12.8-fold for CoronaVac, 16.5-fold for ZF2001, and 5.0-fold for intramuscular Ad5-nCoV. Aerosolized Ad5-nCoV booster also produced the greatest spike-specific B cell response. Our findings suggest that inactivated vaccine recipients should consider adenovirus-vectored vaccine boosters in China and that aerosolized Ad5-nCoV may provide a more efficient alternative in response to the spread of the Omicron variant.

Article activity feed

  1. SciScore for 10.1101/2022.03.08.22271816: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: The protocol was approved by the Ethics Committee of 305 Hospital of PLA.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    RBD-binding IgG assay: RBD-binding IgG antibodies in the heat-inactivated human serum samples and the culture supernatant of PBMCs stimulated for 4 days with R848 + IL-2 were detected with an RBD-binding IgG ELISA kit (Beijing, Kewei).
    RBD-binding IgG
    suggested: None
    The total anti-RBD IgG antibody levels were quantitated in ELISA units (EU) ml-1 by comparison to a reference standard curve created from monoclonal antibodies against SARS-CoV-2 RBD.
    anti-RBD IgG
    suggested: None
    PVDF ELISpot plates were coated with a purified anti-human IgG monoclonal antibody (MT91/145), incubated at 4-8 °C overnight, and blocked with RPMI 1640 medium containing 10% fetal bovine serum and 1× penicillin–streptomycin solution (Gibco) for at least 30 min at room temperature.
    anti-human IgG
    suggested: (GenWay Biotech Inc. Cat# 20-272-192774-0.5 ml, RRID:AB_1984561)
    IFNγ spots were detected after the addition of a biotinylated detection antibody (7-B6-1-biotin, 1 μg ml-1) followed by streptavidin-HRP and TMB substrate.
    7-B6-1-biotin
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    HEK293T cells were cotransfected with the plasmids pNL4.3-Luc-R-E- and pCAGGS-SWT or pCAGGS-SOmicron with TurboFect transfection reagent (Thermo Scientific).
    HEK293T
    suggested: None
    Each sample was serially diluted 3-fold in duplicate from 1:30 to 1:7290 or 1:21870 in complete DMEM before incubation with the titrated pseudovirus SARS-CoV-2 for 1 hour prior to the addition of 2×104 293T-ACE2 cells.
    293T-ACE2
    suggested: None
    Recombinant DNA
    SentencesResources
    HEK293T cells were cotransfected with the plasmids pNL4.3-Luc-R-E- and pCAGGS-SWT or pCAGGS-SOmicron with TurboFect transfection reagent (Thermo Scientific).
    pNL4.3-Luc-R-E-
    suggested: None
    pCAGGS-SWT
    suggested: None
    pCAGGS-SOmicron
    suggested: None
    Software and Algorithms
    SentencesResources
    The results were analyzed by GraphPad Prism 8.0.2 using 4-PL curve fitting.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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:
    There are some limitations to this study. First, we have not yet developed appropriate assays for mucosal immune responses to deepen our understanding of the immune advantage of aerosolized Ad5-nCoV. Saliva IgA antibodies were detected in some BNT162b2 vaccine recipients(25, 26), but whether IgA was exuded from serum or produced by a local mucosal immune response could not be determined. More assays need to be developed to analyze local mucosal immune responses, including secretory IgA antibodies and local cellular immune responses. Second, we assessed immunogenicity 28 days after booster vaccination, but further development of the immune response and the longevity of the responses remain to be evaluated. The half-life of serum neutralizing antibodies was 69-173 days for two-dose mRNA vaccine recipients and 103 days for SARS-CoV-2 convalescents(27-29). The long-term antibody dynamics of neutralizing antibodies after the booster vaccination should be further investigated. In summary, in the face of waning immunity and the circulation of SARS-CoV-2 variants, neutralizing antibody and T-cell responses were boosted most efficiently with aerosolized Ad5-noV in those who received inactivated vaccines as initial doses. Boosters probably increase vaccine effectiveness against infection with and transmission of the SARS-CoV-2 Omicron variant.

    Results from TrialIdentifier: No clinical trial numbers were referenced.


    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.


    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.