The Pilot Study of Immunogenicity and Adverse Events of a COVID-19 Vaccine Regimen: Priming with Inactivated Whole SARS-CoV-2 Vaccine (CoronaVac) and Boosting with the Adenoviral Vector (ChAdOx1 nCoV-19) Vaccine

  1. Surakameth Mahasirimongkol
  2. Athiwat Khunphon
  3. Oraya Kwangsukstid
  4. Sompong Sapsutthipas
  5. Mingkwan Wichaidit
  6. Archawin Rojanawiwat
  7. Nuanjun Wichuckchinda
  8. Wiroj Puangtubtim
  9. Warangluk Pimpapai
  10. Sakulrat Soonthorncharttrawat
  11. Asawin Wanitchang
  12. Anan Jongkaewwattana
  13. Kanjana Srisutthisamphan
  14. Daraka Phainupong
  15. Naphatcha Thawong
  16. Pundharika Piboonsiri
  17. Waritta Sawaengdee
  18. Thitiporn Somsaard
  19. Kanokphon Ritthitham
  20. Supaporn Chumpol
  21. Nadthanan Pinyosukhee
  22. Rattanawadee Wichajarn
  23. Panadda Dhepakson
  24. Sopon Iamsirithaworn
  25. Supaporn Phumiamorn

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Abstract

In response to the SARS-CoV-2 Delta variant, which partially escaped the vaccine-induced immunity provided by two doses of vaccination with CoronaVac (Sinovac), the National Vaccine Committee recommended the heterologous CoronaVac-ChAdOx1 (Oxford–AstraZeneca), a prime–boost vaccine regimen. This pilot study aimed to describe the immunogenicity and adverse events of the heterologous CoronaVac-ChAdOx1 regimen, in comparison with homologous CoronaVac, and homologous ChAdOx1. Between May and August 2021, we recruited a total of 354 participants from four vaccination groups: the CoronaVac-ChAdOx1 vaccinee (n = 155), the homologous CoronaVac vaccinee (n = 32), the homologous ChAdOx1 vaccinee (n = 47), and control group of COVID-19 patients (n = 120). Immunogenicity was evaluated by measuring the level of IgG antibodies against the receptor-binding domain (anti-SRBD) of the SARS-CoV-2 spike protein S1 subunit and the level of neutralizing antibodies (NAbs) against variants of concern (VOCs) using the plaque reduction neutralization test (PRNT) and pseudovirus neutralization test (pVNT). The safety profile was recorded by interviewing at the 1-month visit after vaccination. The anti-SRBD level after the second booster dose of the CoronaVac-ChAdOx1 group at 2 weeks was higher than 4 weeks. At 4 weeks after the second booster dose, the anti-SRBD level in the CoronaVac-ChAdOx1 group was significantly higher than either homologous CoronaVac, the homologous ChAdOx1 group, and Control group (p < 0.001). In the CoronaVac-ChAdOx1 group, the PRNT50 level against the wild-type (434.5 BAU/mL) was the highest; followed by Alpha variant (80.4), Delta variant (67.4), and Beta variant (19.8). The PVNT50 level was also found to be at its highest against the wild-type (432.1); followed by Delta variants (178.3), Alpha variants (163.9), and Beta variant (42.2), respectively. The AEs in the CoronaVac-ChAdOx1 group were well tolerated and generally unremarkable. The CoronaVac-ChAdOx1 heterologous regimen induced higher immunogenicity and a tolerable safety profile. In a situation when only CoronaVac-ChAdOx1 vaccines are available, they should be considered for use in responding to the Delta variant.

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  1. Version published to 10.3390/vaccines10040536
  2. Version published to 10.1101/2021.11.05.21264700v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.11.05.21264700: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The ethical approval of this study was approved by the ethical committee of the Department of Medical Sciences with approval number; MOPH 0625/EC060.
    Consent: Written informed consent was obtained from all participants.
    Field Sample Permit: Pseudotype-Based Microneutralization Assay against SARS-CoV-2: Pseudotype-Based Microneutralization Assay was carried out at the viral vaccine research center, National center for sciences and technology (NSTDA)
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Quantification of SARS-CoV-2 anti-S RBD antibody: The level of immunoglobulin class G (IgG) antibodies to the receptor-binding domain (RBD) of S1 subunit spike protein of SARS-CoV-2 was measured and quantified in human serum or plasma by using the ARCHITECT System (Abbott, Abbott Park, Illinois, USA) chemiluminescent microparticle immunoassay (CMIA) (
    anti-S
    suggested: None
    immunoglobulin class G ( IgG
    suggested: (GeneTex Cat# GTX14582, RRID:AB_370592)
    Based on the evaluated dilutions of the World Health Organization (WHO) International Standard (NIBSC Code 20-136) for anti-SARS-CoV-2 human immunoglobulin in WHO binding antibody unit (WHO BAU/mL) with the SARS-CoV-2 IgG II Quant assay with Abbott internal reference calibrators, the correlation between relationships of the AU/mL unit to the WHO (BAU/mL unit is at 0.142 × AU/mL) with the 0.999 correlation coefficient.
    anti-SARS-CoV-2
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Pseudotyped viruses (PVs) were produced in HEK293T/17 cells.
    HEK293T/17
    suggested: ATCC Cat# CRL-11268, RRID:CVCL_1926)
    Subsequently, HEK293T cells stably expressing human ACE2 and TMPRSS2 (1.5 ×104 cells/well) were mixed with the PV-serum complex before incubation in a humidified cell-culture incubator for 48 h at 37 °C in 5% CO2.
    HEK293T
    suggested: None
    After removing the culture medium from Vero cell culture plates, 200 ul of the virus-serum antibody mixture were inoculated into monolayer cells and then rocked the culture plates every 15 min for 1 h.
    Vero
    suggested: None
    Recombinant DNA
    SentencesResources
    HEK293T/17 producer cells were sub-cultured in 6-well plates (Thermo Fisher Scientific, Waltham, MA, USA) and co-transfected at 80-90% confluence with the p8.91 lentiviral packaging plasmid (500 ng), the pCSFLW firefly luciferase reporter plasmid (1 µg), and the pCAGGS plasmid encoding codon-optimized SARS-CoV-2 spike (1.5µg)10.
    p8.91
    suggested: None
    pCSFLW firefly luciferase reporter
    suggested: None
    pCAGGS
    suggested: RRID:Addgene_18926)
    Software and Algorithms
    SentencesResources
    Quantification of SARS-CoV-2 anti-S RBD antibody: The level of immunoglobulin class G (IgG) antibodies to the receptor-binding domain (RBD) of S1 subunit spike protein of SARS-CoV-2 was measured and quantified in human serum or plasma by using the ARCHITECT System (Abbott, Abbott Park, Illinois, USA) chemiluminescent microparticle immunoassay (CMIA) (
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    Analysis was performed by non-linear regression after normalization to 100% and 0% neutralization using GraphPad Prism Software.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Statistical analysis: All the statistical analyses were performed using R (version 4.0.2) 11 and Rstudio (version 1.3.1093)12.
    Rstudio
    suggested: (RStudio, RRID:SCR_000432)

    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 several limitations to our research. First, our study did not collect comparison data on immunity levels at baseline before the study and after the first vaccine dose, hence, we could not exclude the effect of the previous infection on immunogenicity. However, the COVID-19 infection rate in Thailand was low before July 2021, there is a small possibility to include previously infected COVID-19 cases but these individuals should not affect the immunogenicity results in this study due to the immunity induced by infection were much higher in previously infected individuals compared with single-dose vaccination. A larger sample size is needed to detect uncommon adverse events such as vaccine-induced thrombotic thrombocytopenia and further studies should be done at the time of implementation of this vaccine schedule in the national vaccine program. Moreover, the PRNT50 and PVNT50 were assessed only in I/V regimen, limiting the comparability of the I/V regimen with other vaccine schedules, also the limited time for this study resulted in a smaller sample size that had neutralizing activities, however, the high level of neutralizing antibody suggested that the number of sample size is sufficient for the conclusion that I/V schedule is better than I/I schedule and comparable to V/V schedule. Finally, our research offers crucial real-world proof of the safety and immunogenicity of heterologous CoronaVac-ChAdOx1 nCoV-19 immunization. The I/V vaccination is a mixed regimen that...

    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.

  4. Version published to 10.1101/2021.11.05.21264700v1 on medRxiv