Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes a variety of clinical manifestations, many of which originate from altered immune responses, either locally or systemically. Immune cell cross-talk occurs mainly in lymphoid organs. However, systemic cell interaction specific to coronavirus disease 2019 has not been well characterized. Here, by employing single-cell RNA sequencing and imaging flow cytometry analysis, we unraveled, in peripheral blood, a heterogeneous group of cell complexes formed by the adherence of CD14+ monocytes to different cytotoxic lymphocytes, including SARS-CoV-2-specific CD8+ T cells, γδ T cells, and natural killer T cells. These lymphocytes attached to CD14+ monocytes that showed enhanced inflammasome activation and pyroptosis-induced cell death in progression stage; in contrast, in the convalescent phase, CD14+ monocytes with elevated antigen presentation potential were targeted by cytotoxic lymphocytes, thereby restricting the excessive immune activation. Collectively, our study reports previously unrecognized cell-cell interplay in the SARS-CoV-2-specific immune response, providing new insight into the intricacy of dynamic immune cell interaction representing antiviral defense.

The emergence of SARS-CoV-2 variant of concern omicron BA.2 led to high in-fection incidence rates as well as reduced severity of COVID-19 during the Shang-hai Spring epidemic of 2022[1].We as-sessed the role of viral pathogenicity and the effectiveness of inactivated vaccines in a retrospective observational study including 10 258 confirmed COVID-19 cases identified between April and June of 2022,from four COVID-19 desig-nated hospitals located in two areas of Shanghai,namely the West Bund and the East Bund,where the populations'de-mographic characteristics varied signifi-cantly(Table S1,Fig.S1).

3D Model CD8+ T Cells In article 2200264, Wenguo Cui, Ying Wang, Shun Lu, and co-workers established a tumor-immune microenvironment (TIME) mimicking a hydrogel-based 3D microsphere co-culturing system (3D-HYGTIC). During long-term co-culturing, a step-wise upregulation of key immune checkpoints with spatial heterogeneity in 3D-HYGTIC is observed, which is verified in patient-derived organoids and TIME in the murine model as well. We also presented lymphocyte-activation gene 3 (LAG-3) as a potential nivolumab-resistant target for combinational immunotherapy target in 3D-HYGTIC.

The constant emergence of breakthrough infections with Omicron variants poses an escalating challenge to the current vaccination strategy. In this study, we investigated the distinct neutralization activities and clinical characteristics of the booster vaccinees with Omicron reinfection compared with single breakthrough infection and homologous booster vaccination. Our results demonstrate that neutralizing antibody GMTs for WT and other four subvariants (BA.2.2, BA.5.2, BF.7, and XBB.1) differ greatly between breakthrough infection and homologous booster cohorts. Sequential reinfection with Omicron variants elicits broader and high-titer variant-specific neutralizing antibody profiles against Omicron variants. It could also dampen the hyperactivation of WT-specific neutralization induced by previous WT-based vaccination. Moreover, the clinical characteristics from reinfection demonstrated that repeated stimulation by Omicron variants could reduce the duration of viral shedding. By considering reinfection with the Omicron variant as a representative model of repeated immunogen exposures, our results thus illustrate the potential superiority of repeated Omicron stimuli and provide additional evidence supporting the Omicron immunogen as a more effective vaccine candidate to mitigate the transmission of emerging variants.

The unique degradability and excellent biocompatibility make silk fibroin an attractive material for flexible transient memristors. Materials functionalization from the mesoscopic reconstruction view is a promising route to expand functions and create new types of electronic devices. Here, the transformation of the abrupt-to-progressive switching behavior in fibroin-based memristors is achieved via annealing to adjust the mesoscopic structure. Through electrical test and scanning electron microscope analysis, we study the electrochemical dynamics of metal nanoparticles in switching medium with different mesoscopic structures and directly reveal the microscopic origin of the abrupt-to-progressive transformation in fibroin-based transient memristors. The device exhibits abrupt resistive switching behaviors when the mobility and redox rate are high and displays progressive resistive switching behaviors under the low mobility and low redox rate condition. These findings reveal the microscopic origins of abrupt-to-progressive conversion and provide general guidance for designing high-performance memory devices and artificial synapses.

Background: Variants-of-Concern (VOC) of severe respiratory syndrome coronavirus 2 (SARS-CoV-2) are prevailing sequentially worldwide including China. How BBIBP-CorV vaccination affecting dynamic profiles of antibody responses during Omicron epidemic and their associations with clinical outcomes are investigated in this study.Methods: We carried out a retrospective study in one of the main COVID-19 referral hospitals in Shanghai during March to June, 2022. We recruited 440 COVID-19 in-patient patients in this study and collected the sera to detect antibody levels targeting spike protein receptor binding domain (RBD) and nucleoprotein (N) of both wild type (WT) and Omicron by ELISA. The associations between antibody levels and BBIBP-CorV vaccination as well as clinical outcomes were analyzed.Findings: Enrolled COVID-19 patients (median age 70, range 22-101) were subgrouped into asymptomatic, mild, moderate and severe diseases, among whom severe COVID-19 only occurred in non-vaccinated groups. Vaccinated patients exhibited higher anti-RBD IgG targeting both WT and Omicron than non-vaccinated patients in total as well as at different disease stages. By using a 3-day moving average analysis, we found that BBIBP-CorV vaccinated patients exhibited the increases in both anti-WT and Omicron RBD IgG from the onset of the disease and reached the plateau at Day 8 whereas those in non-vaccinated patients remained at dramatically low levels during the disease durations. Significant increase in anti-WT RBD IgA was observed only in vaccinated patients when compared to non-vaccinated patients as well among which 3-dose vaccinated patients exhibited rapid increase from the onset of the disease, and anti-WT RBD IgA remained at very low levels in 2-dose vaccinated patients until Day 5. Anti-Omicron RBD IgA levels were low in both vaccinated and non-vaccinated patients along the disease processes with moderate increase at the late stage in 3-dose vaccinated COVID-19 patients. Anti-RBD IgG and IgA targeting both WT and Omicron were negatively correlated with viral load, hospitalization days and virus elimination with more extent in vaccinated patients.Interpretation: BBIBP-CorV vaccination effectively reduces the severity rate of Omicron infected COVID-19 patients, which might be associated with rapid induction of both anti-WT and Omicron antibody responses. Our study highlights the existence of cross-reactivity between different SARS-CoV-2 isolates and provides the evidence on extensive cross-protection for VOC through BBIBP-CorV vaccination.Funding Information: This work is financially supported by the grants from National Key Research and Development Program of China (2021YFC2301500), Science and Technology Commission of Shanghai Municipality (20JC14120204), Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases (20dz2261100), the Infectious and Critical Disease Treatment Capacity Promotion Project fund (No. CRZZ202001) from Shanghai Institute of Precision Medicine (Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine), and the SII Challenge Fund for COVID-19 Research.Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: This study was approved by the Ethics Committee of Shanghai Ninth People’s Hospital (SH9H-2022-T111-3). Since serum samples used in this study were those discarded after routine clinical laboratory test, written informed consent was waived according to the ethical report. All the procedures were conducted in accordance with the Declaration of Helsinki.

Previously reported photoelectric devices have mainly been limited to inorganic materials. Even though preparing high-performance photoelectric devices with organic biomaterials is an inevitable trend in commercialization, fabricating organic photoelectric devices based on naturally occurring materials with high sensitivity remains a great challenge due to the high resistivity of and few free electrons in these materials. Herein, high-performance photoelectric devices based on an egg albumin (EA)/Si structure are proposed, and a new, to the best of our knowledge, perspective is provided on photodetection in naturally occurring materials by utilizing the surface state of p-Si to separate light-induced carriers effectively. The free electrons of metal atoms restrain the surface states, leading to a sensitivity of 5 mV/mm for metal/Si devices, while the sensitivity of the EA/Si device in the near-infrared region is greatly promoted to 357 mW/mm, which is intimately related to the lack of effect of EA on the dangling bonds of the surface. The EA/Si device is among the most sensitive organic near-infrared photoelectronic device to date. This work opens up new avenues to overcome the obstacle of the low sensitivity of organic photodetectors, indicating that the EA/Si device has great potential for future applications in flexible photovoltaic devices.

BBIBP-CorV exerts efficient protection against SARS-CoV-2 infection. However, waning vaccine-induced humoral immune responses after two-dose vaccination have significantly undermined durable immuno-protection. In this study, we have demonstrated that although anti-spike (S) antibody responses in BBIBP-CorV vaccinees exhibited three serotypes after 6 months, including de novo sero-negative, sero-positive, and sero-decay features, S-specific interferon-γ release as well as Th1 cytokine production in CD4+ and CD8+ T cells were comparable, especially in vaccinees without detectable neutralizing antibodies. Notably, regardless of dramatic increases in humoral immunity after booster vaccination, T cell responses targeting S protein from either wild type or Omicron remained stable before and after booster vaccination in all three serotype vaccinees. No severe cases were observed even in the sero-decay group during the Omicron epidemic in Shanghai. Our results thus illustrate that unlike fluctuating humoral responses, viral-specific T cell responses are extremely stable after booster vaccination. Sustained T cell responses might be dedicated to the rapid restoration of antibody responses after booster vaccination.

Successfully combating the COVID-19 pandemic depends on mass vaccination with suitable vaccines to achieve herd immunity. Here, we describe COVI-VAC, the only live attenuated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine currently in clinical development. COVI-VAC was developed by recoding a segment of the viral spike protein with synonymous suboptimal codon pairs (codon-pair deoptimization), thereby introducing 283 silent (point) mutations. In addition, the furin cleavage site within the spike protein was deleted from the viral genome for added safety of the vaccine strain. Except for the furin cleavage site deletion, the COVI-VAC and parental SARS-CoV-2 amino acid sequences are identical, ensuring that all viral proteins can engage with the host immune system of vaccine recipients. COVI-VAC was temperature sensitive in vitro yet grew robustly (>107 plaque forming units/mL) at the permissive temperature. Tissue viral loads were consistently lower, lung pathology milder, and weight loss reduced in Syrian golden hamsters (Mesocricetus auratus) vaccinated intranasally with COVI-VAC compared to those inoculated with wild-type (WT) virus. COVI-VAC inoculation generated spike IgG antibody levels and plaque reduction neutralization titers similar to those in hamsters inoculated with WT virus. Upon challenge with WT virus, COVI-VAC vaccination reduced lung challenge viral titers, resulted in undetectable virus in the brain, and protected hamsters from almost all SARS-CoV-2-associated weight loss. Highly attenuated COVI-VAC is protective at a single intranasal dose in a relevant in vivo model. This, coupled with its large-scale manufacturing potential, supports its potential use in mass vaccination programs.

Anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis is a type of autoimmune encephalitis characterized by the rapid onset of neurologic dysfunction. Several studies have reported the important role of post-infectious effect in its pathogenesis. Herein, we report on a 68-year-old woman diagnosed with anti-NMDA receptor encephalitis with concomitant intracranial cryptococcal infection, who was followed up for two years and demonstrated clinical improvements after effective anti-fungal therapy. This case may help expand the clinical spectrum of post-infectious immune-mediated etiology of anti-NMDA receptor encephalitis. The pathogenic role of both disorders requires further investigation.

Abstract Background The WHO estimates that there may be 50 million cases of dengue virus (DENV) infection worldwide every year. There is no safe vaccine against DENV licensed in the United States. The development of a balanced and effective anti-DENV vaccine is vital to preventing morbidity and mortality. Codagenix used its proprietary SAVE (Synthetic Attenuated Virus Engineering) platform to generate and test a live attenuated, tetravalent vaccine against DENV. Methods Codagenix used SAVE to substitute under-represented human codons and codon-pairs into the E protein sequences of contemporary strains of DENV1-4, producing either a fully human-cell-deoptimized prM-E (E-Min), or a partially deoptimized prM-E (E-W/Min) to allow for balancing of the vaccine’s immunogenicity. Full genomes containing deoptimized E-Min and E-W/Min in the DENV2 backbone were transfected into cells to recover live-attenuated, human-cell-deoptimized vaccine strains. Mice were vaccinated with 106 FFU of each DENV vaccine (alone or together), boosted on day 21 and assessed for neutralizing antibodies by PRNT50 and survival after lethal challenge with mouse-adapted wild-type (WT) DENV. Cynomolgus macaques were immunized with a mixture of 106 FFU of each DENV vaccine strain. Two doses were administered on study day 1 and 57 and serum neutralizing antibodies were determined on day 57 and 85 by a microneutralization assay. Results SAVE deoptimized DENV viruses grew to wild-type (between 107 and 108 FFU/ml) levels at permissive temperatures (<37C). All vaccine strains generated neutralizing antibody levels comparable to WT. A tetravalent formulation containing all four E-Min strains protected mice from lethal challenge with DENV3. A tetravalent formulation of Codagenix DENV-E-W/Min vaccine elicited a robust and balanced neutralizing antibody response in non-human primates (NHPs) against all four DENV serotypes after a single dose. A second vaccine dose did not boost antibody titers significantly. Conclusion The ability to rationally balance the attenuation of multiple vaccine strains, thereby avoiding antibody-dependent enhancement, is a unique advantage of the Codagenix SAVE platform. Codagenix DENV vaccine viruses generated balanced, sterilizing immunity in NHPs after one dose. Disclosures All authors: No reported disclosures.