Waning immune responses against SARS-CoV-2 among vaccinees in Hong Kong
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Abstract
Background
Nearly 4 billion doses of the BioNTech-mRNA and Sinovac-inactivated vaccines have been administrated globally, yet different vaccine-induced immunity against SARS-CoV-2 variants of concern (VOCs) remain incompletely investigated.
Methods
We compare the immunogenicity and durability of these two vaccines among fully vaccinated Hong Kong people.
Findings
Standard BioNTech and Sinovac vaccinations were tolerated and induced neutralizing antibody (NAb) (100% and 85.7%) and spike-specific CD4 T cell responses (96.7% and 82.1%), respectively. The geometric mean NAb IC 50 and median frequencies of reactive CD4 subsets were consistently lower among Sinovac-vaccinees than BioNTech-vaccinees. Against VOCs, NAb response rate and geometric mean IC 50 against B1.351 and B.1.617.2 were significantly lower for Sinovac (14.3%, 15 and 50%, 23.2) than BioNTech (79.4%, 107 and 94.1%, 131). Three months after vaccinations, NAbs to VOCs dropped near to detection limit, along with waning memory T cell responses, mainly among Sinovac-vaccinees.
Interpretation
Our results indicate that Sinovac-vaccinees may face higher risk to pandemic VOCs breakthrough infection.
Funding
This study was supported by the Hong Kong Research Grants Council Collaborative Research Fund (C7156-20GF to Z.C and C1134-20GF); the National Program on Key Research Project of China (Grant 2020YFC0860600, 2020YFA0707500 and 2020YFA0707504); Shenzhen Science and Technology Program (JSGG20200225151410198 and JCYJ20210324131610027); HKU Development Fund and LKS Faculty of Medicine Matching Fund to AIDS Institute; Hong Kong Innovation and Technology Fund, Innovation and Technology Commission and generous donation from the Friends of Hope Education Fund. Z.C.’s team was also partly supported by the Theme-Based Research Scheme (T11-706/18-N).
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SciScore for 10.1101/2021.12.22.473934: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: This study was approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster (Ref No. UW 21-452).
Consent: Written informed consent was obtained from all study subjectsSex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources The 50% inhibitory concentrations (IC50) of each specimen were calculated using non-linear regression in GraphPad Prism v8 to reflect anti-SARS-CoV-2 antibody potency. anti-SARS-CoV-2suggested: NoneExperimental Models: Cell Lines Sentences Resources Briefly, SARS-CoV-2 … SciScore for 10.1101/2021.12.22.473934: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: This study was approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster (Ref No. UW 21-452).
Consent: Written informed consent was obtained from all study subjectsSex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources The 50% inhibitory concentrations (IC50) of each specimen were calculated using non-linear regression in GraphPad Prism v8 to reflect anti-SARS-CoV-2 antibody potency. anti-SARS-CoV-2suggested: NoneExperimental Models: Cell Lines Sentences Resources Briefly, SARS-CoV-2 pseudoviruses were generated by co-transfection of 293T cells with a pair of plasmids, the S-expression plasmid for wildtype or VOCs and the pNL4-3Luc_Env_Vpr plasmid in a human immunodeficiency virus type 1 backbone (15, 16). 293Tsuggested: NoneThe plasma-virus mixtures were then added into pre-seeded HEK 293T-hACE2 cells. HEK 293T-hACE2suggested: NoneRecombinant DNA Sentences Resources Briefly, SARS-CoV-2 pseudoviruses were generated by co-transfection of 293T cells with a pair of plasmids, the S-expression plasmid for wildtype or VOCs and the pNL4-3Luc_Env_Vpr plasmid in a human immunodeficiency virus type 1 backbone (15, 16). pNL4-3Luc_Env_Vprsuggested: NoneSoftware and Algorithms Sentences Resources Study subjects: Participants who completed two doses of SARS-CoV-2 vaccination (either BioNTech or Sinovac) before June 2021 were recruited for this study. BioNTechsuggested: NoneFor intracellular staining, cells were fixed and permeabilized with BD Cytofix/Cytoperm (BD Biosciences) prior to staining with the mAbs against cytokines (PE anti-IFN-γ, AF488 anti-TNF-α and PE-Cy7 anti-IL-2) (Biolegend) with Perm/Wash buffer (BD Biosciences). BD Cytofix/Cytopermsuggested: NoneStatistical analysis: Flow cytometric data were analysed using FlowJo 10.6.0. FlowJosuggested: (FlowJo, RRID:SCR_008520)Statistical analysis was performed using the GraphPad Prism v8 Software. GraphPad Prismsuggested: (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:This study has some limitations. Due to lack of a spreading epidemic in Hong Kong, we could not determine vaccine-mediated protective efficacy. The sample size of this study was relatively small and most of our subjects have not reached 6 months for follow-up testing. Extend the follow-up to 6 months and one year or longer is necessary for future study. While NAbs have been indicated as correlates of protection (23, 30), the protective role of vaccine-induced T cell responses remains to be further investigated. During acute SARS-CoV-2 infection, we and others demonstrated that antigen-specific T cell responses have likely been associated with viral control and limited pathogenesis(13) (38). In this study, while we consistently found antigen-specific CD4+T cells after vaccinations by both types of vaccines as previously reported by others (19, 39, 40), majority of our subjects did not show measurable RBD-specific CD4+ T cells. The difference between spike- and RBD-specific CD4 responses and why only spike-specific CD4 responses correlated to NAbTs but not to CD8+ T cells remain unclear. VOC spike-specific T cell responses were not explored due to limited cells received, although some studies indicated that the mutations in VOCs might modify single T cell specificities but could not fully escape the whole repertoire of spike-specific T cells (41, 42). Future studies are needed to address these limitations.
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.
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