Immune response and homeostasis mechanism following administration of BBIBP-CorV SARS-CoV-2 inactivated vaccine.

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.

Human infection of avian influenza A H3N8 virus and the viral origins: a descriptive study.

BACKGROUND: The H3N8 avian influenza virus (AIV) has been circulating in wild birds, with occasional interspecies transmission to mammals. The first human infection of H3N8 subtype occurred in Henan Province, China, in April, 2022. We aimed to investigate clinical, epidemiological, and virological data related to a second case identified soon afterwards in Hunan Province, China. METHODS: We analysed clinical, epidemiological, and virological data for a 5-year-old boy diagnosed with H3N8 AIV infection in May, 2022, during influenza-like illness surveillance in Changsha City, Hunan Province, China. H3N8 virus strains from chicken flocks from January, 2021, to April, 2022, were retrospectively investigated in China. The genomes of the viruses were sequenced for phylogenetic analysis of all the eight gene segments. We evaluated the receptor-binding properties of the H3N8 viruses by using a solid-phase binding assay. We used sequence alignment and homology-modelling methods to study the effect of specific mutations on the human receptor-binding properties. We also conducted serological surveillance to detect the H3N8 infections among poultry workers in the two provinces with H3N8 cases. FINDINGS: The clinical symptoms of the patient were mild, including fever, sore throat, chills, and a runny nose. The patient's fever subsided on the same day of hospitalisation, and these symptoms disappeared 7 days later, presenting mild influenza symptoms, with no pneumonia. An H3N8 virus was isolated from the patient's throat swab specimen. The novel H3N8 virus causing human infection was first detected in a chicken farm in Guangdong Province in December, 2021, and subsequently emerged in several provinces. Sequence analyses revealed the novel H3N8 AIVs originated from multiple reassortment events. The haemagglutinin gene could have originated from H3Ny AIVs of duck origin. The neuraminidase gene belongs to North American lineage, and might have originated in Alaska (USA) and been transferred by migratory birds along the east Asian flyway. The six internal genes had originated from G57 genotype H9N2 AIVs that were endemic in chicken flocks. Reassortment events might have occurred in domestic ducks or chickens in the Pearl River Delta area in southern China. The novel H3N8 viruses possess the ability to bind to both avian-type and human-type sialic acid receptors, which pose a threat to human health. No poultry worker in our study was positive for antibodies against the H3N8 virus. INTERPRETATION: The novel H3N8 virus that caused human infection had originated from chickens, a typical spillover. The virus is a triple reassortment strain with the Eurasian avian H3 gene, North American avian N8 gene, and dynamic internal genes of the H9N2 viruses. The virus already possesses binding ability to human-type receptors, though the risk of the H3N8 virus infection in humans was low, and the cases are rare and sporadic at present. Considering the pandemic potential, comprehensive surveillance of the H3N8 virus in poultry flocks and the environment is imperative, and poultry-to-human transmission should be closely monitored. FUNDING: National Natural Science Foundation of China, National Key Research and Development Program of China, Strategic Priority Research Program of the Chinese Academy of Sciences, Hunan Provincial Innovative Construction Special Fund: Emergency response to COVID-19 outbreak, Scientific Research Fund of Hunan Provincial Health Department, and the Hunan Provincial Health Commission Foundation.

One-Year Sustained Cellular and Humoral Immunities in Coronavirus Disease 2019 (COVID-19) Convalescents.

BACKGROUND: The longitudinal antigen-specific immunity in COVID-19 convalescents is crucial for long-term protection upon individual re-exposure to SARS-CoV-2, and even more pivotal for ultimately achieving population-level immunity. We conducted this cohort study to better understand the features of immune memory in individuals with different disease severities at 1 year post-disease onset. METHODS: We conducted a systematic antigen-specific immune evaluation in 101 COVID-19 convalescents, who had asymptomatic, mild, moderate, or severe disease, through 2 visits at months 6 and 12 after disease onset. The SARS-CoV-2-specific antibodies, comprising neutralizing antibody (NAb), immunoglobulin (Ig) G, and IgM, were assessed by mutually corroborated assays (ie, neutralization, enzyme-linked immunosorbent assay [ELISA], and microparticle chemiluminescence immunoassay [MCLIA]). Meanwhile, T-cell memory against SARS-CoV-2 spike, membrane, and nucleocapsid proteins was tested through enzyme-linked immunospot assay (ELISpot), intracellular cytokine staining, and tetramer staining-based flow cytometry, respectively. RESULTS: SARS-CoV-2-specific IgG antibodies, and NAb, can persist among >95% of COVID-19 convalescents from 6 to 12 months after disease onset. At least 19/71 (26%) of COVID-19 convalescents (double positive in ELISA and MCLIA) had detectable circulating IgM antibody against SARS-CoV-2 at 12 months post-disease onset. Notably, numbers of convalescents with positive SARS-CoV-2-specific T-cell responses (≥1 of the SARS-CoV-2 antigen S1, S2, M, and N proteins) were 71/76 (93%) and 67/73 (92%) at 6 and 12 months, respectively. Furthermore, both antibody and T-cell memory levels in the convalescents were positively associated with disease severity. CONCLUSIONS: SARS-CoV-2-specific cellular and humoral immunities are durable at least until 1 year after disease onset.

Immune response pattern across the asymptomatic, symptomatic and convalescent periods of COVID-19.

We present an integrated analysis of urine and serum proteomics and clinical measurements in asymptomatic, mild/moderate, severe and convalescent cases of COVID-19. We identify the pattern of immune response during COVID-19 infection. The immune response is activated in asymptomatic infection, but is dysregulated in mild and severe COVID-19 patients. Our data suggest that the turning point depends on the function of myeloid cells and neutrophils. In addition, immune defects persist into the recovery stage, until 12 months after diagnosis. Moreover, disorders of cholesterol metabolism span the entire progression of the disease, starting from asymptomatic infection and lasting to recovery. Our data suggest that prolonged dysregulation of the immune response and cholesterol metabolism might be the pivotal causative agent of other potential sequelae. Our study provides a comprehensive understanding of COVID-19 immunopathogenesis, which is instructive for the development of early intervention strategies to ameliorate complex disease sequelae.