Project description:The prevalence of SARS-CoV-2 variants of concern (VOCs) is still escalating throughout the world. However, the level of neutralization of the inactivated viral vaccine recipients' sera and convalescent sera against all VOCs, including B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta), and B.1.1.529 (Omicron) remains to be lack of comparative analysis. Therefore, we constructed pseudoviruses of five VOCs using a lentiviral-based system and analyzed their viral infectivity and neutralization resistance to convalescent and BBIBP-CorV vaccinee serum at different times. Our results show that, compared with the wild-type strain (WT), five VOC pseudoviruses showed higher infection, of which B.1.617.2 and B.1.1.529 variant pseudoviruses exhibited higher infection rates than wild-type or other VOC strains, respectively. Sera from 10 vaccinated individuals at the 1, 3 and 5-month post second dose or from 10 convalescent in 14 and 200 days after discharge retained neutralizing activity against all strains but exhibited decreased neutralization activity significantly against the five VOC variant pseudoviruses over time compared to WT. Notably, 100% (30/30) of the vaccinee serum samples showed more than a 2.5-fold reduction in neutralizing activity against B.1.1.529, and 90% (18/20) of the convalescent serum samples showed more than 2.5-fold reduction in neutralization against B.1.1.529. These findings demonstrate the reduced protection against the VOCs in vaccinated and convalescent individuals over time, indicating that it is necessary to have a booster shot and develop new vaccines capable of eliciting broad neutralization antibodies.
Project description:Several observational studies have confirmed that the severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) might substantially affect the gastrointestinal (GI) system by replicating in human small intestine enterocytes. Yet, so far, no study has reported the effects of inactivated SARS-CoV-2 virus vaccines on gut microbiota alterations. In this study, we examined the effects of the BBIBP-CorV vaccine (ChiCTR2000032459, sponsored by the Beijing Institute of Biological Products/Sinopharm), on gut microbiota. Fecal samples were collected from individuals whoreceived two doses of intramuscular injection of BBIBP-CorV and matched unvaccinated controls. DNA extracted from fecal samples was subjected to 16S ribosomal RNA sequencing analysis. The composition and biological functions of the microbiota between vaccinated and unvaccinated individuals were compared. Compared with unvaccinated controls, vaccinated subjects exhibited significantly reduced bacterial diversity, elevated firmicutes/bacteroidetes (F/B) ratios, a tendency towards Faecalibacterium-predominant enterotypes, and altered gut microbial compositions and functional potentials. Specifically, the intestinal microbiota in vaccine recipients was enriched with Faecalibacterium and Mollicutes and with a lower abundance of Prevotella, Enterococcus, Leuconostocaceae, and Weissella. Microbial function prediction by phylogenetic investigation of communities using reconstruction of unobserved states (PICRUSt) analysis further indicated that Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in carbohydrate metabolism and transcription were positively associated with vaccine inoculation, whereas capacities in neurodegenerative diseases, cardiovascular diseases, and cancers were negatively affected by vaccines. Vaccine inoculation was particularly associated with gut microbiota alterations, as was demonstrated by the improved composition and functional capacities of gut microbiota.
Project description:The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens global public health. The development of a vaccine is urgently needed for the prevention and control of COVID-19. Here, we report the pilot-scale production of an inactivated SARS-CoV-2 vaccine candidate (BBIBP-CorV) that induces high levels of neutralizing antibodies titers in mice, rats, guinea pigs, rabbits, and nonhuman primates (cynomolgus monkeys and rhesus macaques) to provide protection against SARS-CoV-2. Two-dose immunizations using 2 μg/dose of BBIBP-CorV provided highly efficient protection against SARS-CoV-2 intratracheal challenge in rhesus macaques, without detectable antibody-dependent enhancement of infection. In addition, BBIBP-CorV exhibits efficient productivity and good genetic stability for vaccine manufacture. These results support the further evaluation of BBIBP-CorV in a clinical trial.
Project description:The BBIBP-CorV severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated vaccine has been authorized for emergency use and widely distributed. We used single-cell transcriptome sequencing to characterize the dynamics of immune responses to the BBIBP-CorV inactivated vaccine. In addition to the expected induction of humoral immunity, we found that the inactivated vaccine induced multiple, comprehensive immune responses, including significantly increased proportions of CD16+ monocytes and activation of monocyte antigen presentation pathways; T cell activation pathway upregulation in CD8+ T cells, along with increased activation of CD4+ T cells; significant enhancement of cell-cell communications between innate and adaptive immunity; and the induction of regulatory CD4+ T cells and co-inhibitory interactions to maintain immune homeostasis after vaccination. Additionally, comparative analysis revealed higher neutralizing antibody levels, distinct expansion of naive T cells, a shared increased proportion of regulatory CD4+ T cells, and upregulated expression of functional genes in booster dose recipients with a longer interval after the second vaccination. Our research will support a comprehensive understanding of the systemic immune responses elicited by the BBIBP-CorV inactivated vaccine, which will facilitate the formulation of better vaccination strategies and the design of new vaccines.
Project description:BBIBP-CorV, an inactivated vaccine, has demonstrated safety, efficacy, and immunogenicity against COVID-19 in in-vitro studies and clinical trials. This study sought to comprehensively understand the development and duration of virus-specific antibodies and characterize the TCR-β repertoire changes in patients with BBIBP-CorV
Project description:ObjectiveTo estimate the prevalence of post-vaccination seropositivity against SARS-CoV-2 and identify its predictors in Peruvian Social Health Insurance (EsSalud) personnel in 2021.MethodsWe conducted a cross-sectional study in a representative simple stratified sample of EsSalud workers. We evaluated IgG anti-SARS-CoV-2 antibodies response (seropositivity) by passive (previous infection) and active immunization (vaccination), and epidemiological and occupational variables obtained by direct interview and a data collection form. Descriptive and inferential statistics were used with correction of sample weights adjusted for non-response rate, and crude and adjusted odds ratio (OR) and geometric mean ratio (GMR) with their respective 95% confidence intervals (95%CI) were estimated.ResultsWe enrolled 1077 subjects. Seropositivity was 67.4% (95%CI: 63.4-71.1). Predictors of seropositivity were age (negative relation; p < 0.001), previous infection (aOR = 11.7; 95%CI: 7.81-17.5), working in COVID-19 area (aOR = 1.47; 95%CI: 1.02-2.11) and time since the second dose. In relation to antibody levels measured by geometric means, there was an association between male sex (aGMR = 0.77; 95%CI: 0.74-0.80), age (negative relation; p < 0.001), previous infection (aGMR = 13.1; 95%CI:4.99-34.40), non-face-to-face/licensed work modality (aGMR = 0.78; 95%CI: 0.73-0.84), being a nursing technician (aGMR = 1.30; 95%CI: 1.20-1.41), working in administrative areas (aGMR = 1.17; 95%CI: 1.10-1.25), diagnostic support (aGMR = 1.07; 95%CI: 1.01-1.15), critical care (aGMR = 0.85; 95%CI: 0.79-0.93), and in a COVID-19 area (aGMR = 1.30; 95%CI: 1.24-1.36) and time since receiving the second dose (negative relation; p < 0.001).ConclusionsSeropositivity and antibody levels decrease as the time since receiving the second dose increases. Older age and no history of previous infection were associated with lower seropositivity and antibody values. These findings may be useful for sentinel antibody surveillance and the design of booster dose strategies.