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.

Seeing the T cell Immunity of SARS-CoV-2 and SARS-CoV: Believing the Epitope-Oriented Vaccines.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the end of 2019 stimulated vigorous research efforts in immunology and vaccinology. In addition to innate immune responses, both virus-specific humoral and cellular immune responses are of importance for viral clearance. T cell epitopes play a central role in T cell-based immune responses. Herein, we summarized the peptide/major histocompatibility complex (pMHC) structures of the SARS-CoV-2-derived T cell epitopes available in the Protein Data Bank (PDB) and proposed the challenge and opportunities for using of T cell epitopes in future vaccine development efforts. A total of 27 SARS-CoV-2 related pMHC structures and five complexes with T cell receptors were retrieved. The peptides are mainly distributed on spike (S), nucleocapsid (N), and ORF1ab proteins. Most peptides are conserved among variants of concerns (VOCs) for SARS-CoV-2, except for several mutated peptides located in the S protein. The structures of human leukocyte antigen (HLA) complexed with seven epitopes derived from SARS-CoV were also retrieved, which showed a potential cross T cell immunity with SARS-CoV-2. Structural studies of antigenic peptides from SARS-CoV-2 and SARS-CoV help to visualize the processes and the mechanisms of cross T cell immunity. T cell epitope-oriented vaccines are potential next-generation vaccines for SARS-CoV-2, which are worthy of further investigation.

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.

Choroidal Circulation in 8- to 30-Year-Old Chinese, Measured by SS-OCT/OCTA: Relations to Age, Axial Length, and Choroidal Thickness.

Purpose: The purpose of this study was to evaluate and explore the determinants of choroidal vascularity and choriocapillaris perfusion in a Chinese population aged 8 to 30 years old. Methods: Three hundred eighty eyes from 380 subjects aged 8 to 30 years were included in this cross-sectional study. Submacular choroidal thickness (ChT), total choroidal area (TCA), luminal area (LA), stromal area (SA), choroidal vascularity index (CVI), and choriocapillaris flow deficit (CcFD) were estimated using images obtained from optical coherence tomography (OCT). Results: In this population, the mean ChT was 260.4 ± 63.3 µm, TCA was 1.56 ± 0.38 mm2, LA was 0.94 ± 0.25 mm2, and SA was 0.62 ± 0.15 mm2. The mean CVI was 60.25 ± 3.21% and CcFD was 11.95 ± 1.98%. Multivariable analyses showed that higher CVI and LA was associated with older age, thicker ChT, and shorter AL; and lower CcFD was associated with shorter AL. However, the associations were not uniformly rectilinear between CcFD and age. Specifically, CcFD was positively associated with age in subjects ≤19 years old and negatively associated with age in subjects >19 years old. Conclusions: Development of the choroidal medium- and large-sized vascular layers and choriocapillaris was different across patients aged 8 to 30 years old. Greater axial length was associated with attenuated choroidal circulation. Choroidal thickness correlated well with choroidal vascularity, but not with choriocapillaris perfusion. Further comprehensive and longitudinal assessment of choroidal vasculature and choriocapillaris perfusion will help greatly to understand the physiological and pathological mechanisms responsible for myopia.

Choroidal blood perfusion could predict the sensitivity of myopia formation in Guinea pigs.

In this study, we explored the predictive role of choroidal blood perfusion (ChBP) and choroidal thickness (ChT) on the development of myopia in guinea pigs. Optical Coherence Tomography Angiography (OCTA) was used to assess the baseline choroidal blood perfusion (ChBP) and choroidal thickness (ChT) in 4-week-old guinea pigs. Refraction and axial length (AL) were measured at baseline. Myopia was induced for one week using form-deprivation (FD) or negative lenses followed by measurements of refraction, axial length and choroidal parameters (ChT and ChBP). The correlations were evaluated between the baseline choroidal values and the magnitude of myopia induced, along with the magnitude of changes in ChT and ChBP after myopia induction. There was a significant correlation between the baseline choroidal parameters and ocular refraction. Myopia induction led to choroidal thinning and less ChBP as well as longer eyes. On the other hand, following exposure to the same non-obstructed visual induction period, the myopic shift was less, and it was associated with thicker choroids and more ChBP at baseline. One week of myopia induction also resulted in thinner choroids and less ChBP, and these declines also correlated with their baseline values. In conclusion, the present study shows that the changes in the baseline choroidal ChT and ChBP parameters are proportional to the magnitude of myopia development and axial elongation in guinea pigs. These significant correlations between baseline ChBP and ChT and myopia development suggest that they may be a viable predictor of this process in guinea pigs.

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.