Th2 cytokines were mainly activated at Day28, Da圓5, and Day45, supporting humoral immune responses at later stages, especially after the second vaccination. Th1 cytokines were mainly activated at Day14, Day28, and Da圓5, supporting cellular immune responses at early stages when the serum neutralizing antibody titer was low. By purifying CD4 +T cells from PBMC and re-stimulating them with CoronaVac in vitro, five cytokines were significantly released, including Th1 cytokines (IFN-γ and IL-2) and Th2 cytokines (IL-4, IL-6, and IL-10). For both vaccinated participants and recovered participants, the upregulated JUN/FOS network and tuned expressions of immunoglobulin fragments such as IGHV3-30 and IGLV2-23 were observed in B cells. The serum neutralizing antibody titer to live SARS-CoV-2 was low within four weeks after the first vaccination, but the second vaccination could induce significantly higher serum neutralizing antibody titers due to the immune memory. The B cell levels in PBMC increased after each vaccination, while the T cell levels mainly increased within four weeks after the first vaccination and peaked at Day28. Gradual transitions of PBMC transcriptomics were observed from Day14 to Day28 and Da圓5 in vaccination groups, which finally approached the recovery control.
For samples from all 25 participants, the serum neutralizing antibody titer to live SARS-CoV-2 and the in vitro cytokine release activity of CD4 +T cells were assayed as immune function responses.įindings: Single-cell RNA sequencing showed that the PBMC transcriptomics after vaccination resembled the COVID-19 recovery control more than that before vaccination, which also applied to its constituent cells such as B cells, T cells, NK cells, and myeloid cells. The transcriptomics of PBMC and its constituent cells were analyzed as gene expression responses. Considering the high cost of sequencing, 11 samples from two healthy participants (H1 and H2) with four timepoints (Day00, Day14, Day28, and Da圓5) and three recovered participants (R1, R2, and R3) with one timepoint (Month8) were randomly chosen for single-cell RNA sequencing of peripheral blood mononuclear cells (PBMC). As positive control, 12 participants aged 28–75 years that had recovered from COVID-19 for approximately eight months were recruited in the recovery group with peripheral blood samples collected. Methods: In this controlled study, 13 healthy participants aged 21–54 years were recruited in the vaccination group and intramuscularly injected with two doses of CoronaVac (3 μg / 0♵ mL per dose, at Day00 and Day28, right after blood sampling), with peripheral blood samples collected at Day00, Day14, Day28, Da圓5, and Day45 to monitor dynamic changes. We investigated the immune mechanisms underlying CoronaVac from the perspective of single-cell gene expressions and immune function features. As a promising inactivated SARS-CoV-2 vaccine, CoronaVac (developed by Sinovac Life Sciences, Beijing, China) is currently undergoing its clinical trials in several countries and showing good results.
For more information on this collaboration, see the comments published in The Lancet about the trial period, and our decision to make this a permanent offering, or visit The Lancet´s FAQ page, and for any feedback please contact Single-Cell Sequencing and Immune Function Assays of Peripheral Blood Samples Demonstrate Positive Responses of an Inactivated SARS-CoV-2 Vaccineīackground: Safe and effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed to halt the spread of coronavirus disease 2019 (COVID-19) pandemic. The findings should not be used for clinical or public health decision making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed. These preprints are early stage research papers that have not been peer-reviewed. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication.