Inactivated vaccine fueled adaptive immune responses to Omicron in 2-year COVID-19 convalescents.

Over 3 years, humans have experienced multiple rounds of global transmission of SARS-CoV-2 and its variants. In addition, the widely used vaccines against SARS-CoV-2 involve multiple strategies of development and inoculation. Thus, the acquired immunity established among humans is complicated, and there is a lack of understanding within a panoramic vision. Here, we provided the special characteristics of the cellular and humoral responses in 2-year convalescents after inactivated vaccines, in parallel to vaccinated COVID-19 naïve persons and unvaccinated controls. The decreasing trends of the IgG, IgA, and NAb, but not IgM of the convalescents were reversed by the vaccination. Both cellular and humoral immunity in convalescents after vaccination were higher than the vaccinated COVID-19 naïve persons. Notably, inoculation with inactivated vaccine fueled the NAb to BA.1, BA.2, BA.4, and BA.5 in 2-year convalescents, much higher than the NAb during 6 months and 1 year after symptoms onset. And no obvious T cell escaping to the S protein was observed in 2-year convalescents after inoculation. The study provides insight into the complicated features of human acquired immunity to SARS-CoV-2 and variants in the real world, indicating that promoting vaccine inoculation is essential for achieving herd immunity against emerging variants, especially in convalescents.

Nonconserved epitopes dominate reverse preexisting T cell immunity in COVID-19 convalescents.

The herd immunity against SARS-CoV-2 is continuously consolidated across the world during the ongoing pandemic. However, the potential function of the nonconserved epitopes in the reverse preexisting cross-reactivity induced by SARS-CoV-2 to other human coronaviruses is not well explored. In our research, we assessed T cell responses to both conserved and nonconserved peptides shared by SARS-CoV-2 and SARS-CoV, identifying cross-reactive CD8+ T cell epitopes using enzyme-linked immunospot and intracellular cytokine staining assays. Then, in vitro refolding and circular dichroism were performed to evaluate the thermal stability of the HLA/peptide complexes. Lastly, single-cell T cell receptor reservoir was analyzed based on tetramer staining. Here, we discovered that cross-reactive T cells targeting SARS-CoV were present in individuals who had recovered from COVID-19, and identified SARS-CoV-2 CD8+ T cell epitopes spanning the major structural antigens. T cell responses induced by the nonconserved peptides between SARS-CoV-2 and SARS-CoV were higher and played a dominant role in the cross-reactivity in COVID-19 convalescents. Cross-T cell reactivity was also observed within the identified series of CD8+ T cell epitopes. For representative immunodominant peptide pairs, although the HLA binding capacities for peptides from SARS-CoV-2 and SARS-CoV were similar, the TCR repertoires recognizing these peptides were distinct. Our results could provide beneficial information for the development of peptide-based universal vaccines against coronaviruses.

Long-lasting humoral and cellular memory immunity to vaccinia virus Tiantan provides pre-existing immunity against mpox virus in Chinese population.

Investigating immune memory to vaccinia virus and pre-existing immunity to mpox virus (MPXV) among the population is crucial for the global response to this ongoing mpox epidemic. Blood was sampled from vaccinees inoculated with vaccinia virus Tiantan (VTT) strain born before 1981 and unvaccinated control subjects born since 1982. After at least 40 years of the inoculation, 60% or 5% VTT vaccinees possess neutralizing antibodies (NAbs) to VTT or MPXV, with at least 50% having T cell memory to VTT protein antigens. Notably, 46.7% vaccinees show pre-existing T cell responses to MPXV. Broad pre-existing CD8+ T cell reactivities to MPXV are detected not only against conserved epitopes but also against variant epitopes between VTT and MPXV. Persistent NAbs and T cell memory to VTT among vaccinees, along with pre-existing T cells to MPXV among both vaccinees and the unvaccinated population, indicate a particular immune barrier to mpox.

The genomic characteristics and pathogenicity of a mammalian orthoreovirus within a new lineage from wild pika in plateau.

Emerging and re-emerging viruses from wild animals have seriously threatened the health of humans and domesticated animals in recent years. Herein, we isolated a new mammalian orthoreovirus (MRV), Pika/MRV/GCCDC7/2019 (PMRV-GCCDC7), in the Qinghai-Tibet Plateau wild pika (Ochotona curzoniae). Though the PMRV-GCCDC7 shows features of a typical reovirus with ten gene segments arranged in 3:3:4 in length, the virus belongs to an independent evolutionary branch compared to other MRVs based on phylogenetic tree analysis. The results of cellular susceptibility, species tropism, and replication kinetics of PMRV-GCCDC7 indicated the virus could infect four human cell lines (A549, Huh7, HCT, and LoVo) and six non-human cell lines, including Vero-E6, LLC-MK2, BHK-21, N2a, MDCK, and RfKT cell, derived from diverse mammals, i.e. monkey, mice, canine and bat, which revealed the potential of PMRV-GCCDC7 to infect a variety of hosts. Infection of BALB/c mice with PMRV-GCCDC7 via intranasal inoculation led to relative weight loss, lung tissue damage and inflammation with the increase of virus titer, but no serious respiratory symptoms and death occurred. The characterization of the new reovirus from a plateau-based wild animal has expanded our knowledge of the host range of MRV and provided insight into its risk of trans-species transmission and zoonotic diseases.

Repeated influenza vaccination induces similar immune protection as first-time vaccination but with differing immune responses.

BACKGROUND: Recent seasonal epidemics of influenza have been caused by human influenza A viruses of the H1N1 and H3N2 subtypes and influenza B viruses. Annual vaccination is recommended to prevent infection; however, how annual influenza vaccination influences vaccine effectiveness is largely unknown. METHODS: To investigate the impact of repeated vaccination on immune and protective effect, we performed a prospective seroepidemiologic study. Participants with or without prior vaccination (2018-2019) were enrolled during the 2019-2020 influenza season. Inactivated quadrivalent influenza vaccine (IIV4) was administered through the intramuscular route, and venous blood samples were collected regularly to test hemagglutination inhibition (HAI) titers. RESULTS: The geometric mean titers and proportion with titers ≥40 against the influenza vaccine components peaked at 30 days post-vaccination. At Day 30, the geometric mean titer and proportion with titers ≥40 in participants who had been previously vaccinated were higher for H3N2 but similar for both B lineages (Victoria and Yamagata) as compared with participants vaccinated for the first time. As for H1N1, the geometric mean titer was lower in repeated vaccinated participants, but the proportion with titers ≥40 was consistent in both groups. CONCLUSIONS: Repeated vaccination provides similar or enhanced protection as compared with single vaccination in first-time vaccinees.

A COVID-19 T-Cell Response Detection Method Based on a Newly Identified Human CD8+ T Cell Epitope from SARS-CoV-2 - Hubei Province, China, 2021.

INTRODUCTION: Similar to antibody detection, severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-specific T-cell response evaluation is also pivotal among the coronavirus disease 2019 (COVID-19) convalescents and the vaccinated populations. Nucleocapsid (N) protein is one of the main structural proteins of SARS-CoV-2 and can trigger T-cell responses in humans. METHODS: An overlapping peptide pool covering the full length of the N protein was designed, peptides with positive T-cell activating potency in COVID-19 convalescents were screened, and CD8+ T cell epitopes were further identified. The epitope was used to detect the SARS-CoV-2-specific CD8+ T cell responses in COVID-19 convalescents based in intracellular cytokine staining and tetramer staining in flow cytometry. RESULTS: A human leukocyte antigen A (HLA-A)*1101-restricted CD8+ T cell epitope, which could stimulate the production of IFN-γ via peripheral blood mononuclear cells (PBMCs) of the convalescents was defined, and the tetramer generated with this epitope could detect SARS-CoV-2-specific T cells in the PBMCs of the convalescents. The structural investigation eliminated that the epitope was a typical HLA-A*1101-restricted T-cell epitope which was conserved among all the sarbecoviruses. DISCUSSION: The newly identified SARS-CoV-2-derived T-cell epitope was helpful to detect the cellular immunity against different sarbecoviruses including SARS-CoV and SARS-CoV-2. This study provided an evaluation method and also a peptide candidate for the research and development of T-cell based vaccine for the virus.