The immunogenicity and reactogenicity of four COVID-19 booster vaccinations against SARS-CoV-2 variants of concerns (Delta, Beta, and Omicron) following CoronaVac or ChAdOx1 nCoV-19 primary series

  1. Nasikarn Angkasekwinai
  2. Suvimol Niyomnaitham
  3. Jaturong Sewatanon
  4. Supaporn Phumiamorn
  5. Kasama Sukapirom
  6. Sansnee Senawong
  7. Zheng Quan Toh
  8. Pinklow Umrod
  9. Thitiporn Somporn
  10. Supaporn Chumpol
  11. Kanokphon Ritthitham
  12. Yuparat Jantraphakorn
  13. Kanjana Srisutthisamphan
  14. Kulkanya Chokephaibulkit

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Abstract

The CoronaVac (Sinovac Biotech) and ChAdOx1(Oxford-AstraZeneca) are two widely used COVID-19 vaccines. We examined the immunogenicity of four COVID-19 booster vaccine: BBIBP-CorV (Sinopharm Biotech), ChAdOx1, 30μg-BNT162b2 and 15μg-BNT162b2 (Pfizer-BioNTech), in healthy adults who received a two-dose CoronaVac or ChAdOx1 8-12 weeks earlier. Among the 352 participants (179 CoronaVac and 173 ChAdOx1 participants), 285 (81%) were female, and median age was 39(IQR: 31-47) years. 98%(175/179) and 99%(172/173) of Coronavac and ChAdOx1 participants remained seropositive at baseline. Two weeks post-booster, both 30μg- and 15μg-BNT162b2 induced the highest anti-RBD IgG concentration (BAU/mL); Coronavac-prime: 30μg-BNT162b2, 5152.2(95%CI 4491.7-5909.8); 15μg-BNT162b2, 3981.1(3397.2-4665.4); ChAdOx1, 1358.0(1141.8-1615.1); BBIBP-CorV, 154.6(92.11-259.47); ChAdOx1-prime: 30μg-BNT162b2, 2363.8(2005.6-2786.1; 15μg-BNT162b2, 1961.9(1624.6-2369.1); ChAdOx1, 246.4(199.6-304.2); BBIBP-CorV, 128.1(93.5-175.4). Similarly, both 30μg- and 15μg-BNT162b2 boosting induced the highest neutralizing antibodies (nAb) titres against all variants and highest T-cell response evaluated by interferon gamma released asssays. While all BNT162b2 or heterologous ChAdOx1-boosted participants had nAb against Omicron, these were <50% for BBIBP-CorV and 75% for homologous ChAdOx1-boosted participants. There was significant decrease in nAb (>4-fold) 16-20 weeks post booster. Heterologous boosting with BNT162b2 following CoronaVac or ChAdOx1 primary series is most immunogenic. A lower dose BNT162b2 may be considered as booster in settings with limited vaccine supply.

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  1. Version published to 10.1101/2021.11.29.21266947v3 on medRxiv
  2. Version published to 10.1101/2021.11.29.21266947v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.11.29.21266947: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: The study procedures, risks, and benefits were explained to all participants before obtaining written informed consent.
    IRB: The study protocol was approved by the Siriraj Institutional Review Board (COA no. Si 537/2021).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Blood samples were collected at baseline (pre-booster), and two weeks after booster vaccination (post-boost) to determine the level of antibody response (IgG) against receptor binding domain (RBD) of the SARS-CoV-2 S1 subunit spike protein (anti-RBD IgG) and 50% plaque reduction neutralisation test (PRNT50) against Delta (B1.1617.2) and Beta (B.1.351) variants.
    IgG) against receptor binding domain (RBD
    suggested: None
    S1 subunit spike protein (anti-RBD IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Vero cells were seeded at 2× 105cells/well/ 3 ml and placed in 37°C, 5% CO2 incubator for 1 day.
    Vero
    suggested: None
    Software and Algorithms
    SentencesResources
    The anti-RBD IgG was quantitatively measured by CMIA using the SARS-CoV-2 IgG II Quant (Abbott, List No. 06S60) on the ARCHITECT i System.
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    Unpaired t-test was used to compare GMC of the IgG concentrations between groups using GraphPad Prism 9 version 9.2.0 (283) (GraphPad Software, CA, USA).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    All statistical analyses were conducted using STATA version
    STATA
    suggested: (Stata, RRID:SCR_012763)

    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 in this study. First, our study was conducted in an open label manner due to the availability of each vaccine at a different timing. While this may lead to selection bias and subjective outcomes such as AEs, the demographic characteristics of the participants in the booster groups were very similar, suggesting that this is unlikely to influence our findings. Second, our sample size is small, particularly those who received BBIBP as booster, and therefore, the data need to be interpreted with caution. Furthermore, it is unclear if similar findings will be found if the duration between the last dose of primary series and the booster dose is >12 weeks (8-12 weeks in this study). Last, the participants in this study were healthy adults therefore results may not be generalisable to other populations such as elderly or those with underlying diseases. In conclusion, we found that a booster dose of BNT162b2 given to individuals previously vaccinated with CoronaVac or ChaAdOx1 primary series is the most immunogenic. Our study findings have important implications on the choice of booster dose following CoronaVac or ChAdOx1 primary series, and are most relevant for countries that have introduced these vaccines to date. Furthermore, our study indicates that reduced dosage of BNT162b2 may be used as a booster dose instead of the standard dosage. This will aid in improving global access to COVID-19 vaccines.

    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

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  4. Version published to 10.1101/2021.11.29.21266947v1 on medRxiv