Improving interface quality for 1-cm2 all-perovskite tandem solar cells.

All-perovskite tandem solar cells provide high power conversion efficiency at a low cost1-4. Rapid efficiency improvement in small-area (<0.1 cm2) tandem solar cells has been primarily driven by advances in low-bandgap (approximately 1.25 eV) perovskite bottom subcells5-7. However, unsolved issues remain for wide-bandgap (> 1.75 eV) perovskite top subcells8, which at present have large voltage and fill factor losses, particularly for large-area (>1 cm2) tandem solar cells. Here we develop a self-assembled monolayer of (4-(7H-dibenzo[c,g]carbazol-7-yl)butyl)phosphonic acid as a hole-selective layer for wide-bandgap perovskite solar cells, which facilitates subsequent growth of high-quality wide-bandgap perovskite over a large area with suppressed interfacial non-radiative recombination, enabling efficient hole extraction. By integrating (4-(7H-dibenzo[c,g]carbazol-7-yl)butyl)phosphonic acid in devices, we demonstrate a high open-circuit voltage (VOC) of 1.31 V in a 1.77-eV perovskite solar cell, corresponding to a very low VOC deficit of 0.46 V (with respect to the bandgap). With these wide-bandgap perovskite subcells, we report 27.0% (26.4% certified stabilized) monolithic all-perovskite tandem solar cells with an aperture area of 1.044 cm2. The certified tandem cell shows an outstanding combination of a high VOC of 2.12 V and a fill factor of 82.6%. Our demonstration of the large-area tandem solar cells with high certified efficiency is a key step towards scaling up all-perovskite tandem photovoltaic technology.

Characterization of linezolid- and methicillin-resistant coagulase-negative staphylococci in a tertiary hospital in China.

BACKGROUND: Recently, linezolid-resistant staphylococci have become an emerging problem worldwide. Understanding the mechanisms of resistance, molecular epidemiology and transmission of linezolid-resistant CoNS in hospitals is very important. METHODS: The antimicrobial susceptibilities of all isolates were determined by the microdilution method. The resistance mechanisms and molecular characteristics of the strains were determined using whole-genome sequencing and PCR. RESULTS: All the strains were resistant to oxacillin and carried the mecA gene; 13 patients (36.1%) had prior linezolid exposure. Most S. epidermidis and S. hominis isolates were ST22 and ST1, respectively. MLST typing and evolutionary analysis indicated most linezolid-resistant CoNS strains were genetically related. In this study, we revealed that distinct CoNS strains have different mechanisms of linezolid resistance. Among ST22-type S. epidermidis, acquisition of the T2504A and C2534T mutations in the V domain of the 23 S rRNA gene, as well as mutations in the ribosomal proteins L3 (L101V, G152D, and D159Y) and L4 (N158S), were linked to the development of linezolid resistance. In S. cohnii isolates, cfr, S158Y and D159Y mutations in the ribosomal protein L3 were detected. Additionally, emergence of the G2576T mutation and the cfr gene were major causes of linezolid resistance in S. hominis isolates. The cfr gene, G2576T and C2104T mutations, M156T change in L3 protein, and I188S change in L4 protein were found in S. capitis isolates. CONCLUSION: The emergence of linezolid-resistant CoNS in the environment is concerning because it involves clonal dissemination and frequently coexists with various drug resistance mechanisms.

Unexpectedly higher levels of anti-orthopoxvirus neutralizing antibodies are observed among gay men than general adult population.

BACKGROUND: The confirmed cases in the current outbreak of Monkeypox are predominantly identified in the networks of men who have sex with men (MSM). The preexisting antibodies may profoundly impact the transmission of monkeypox virus (MPXV), however the current-day prevalence of antibodies against MPXV among gay men is not well characterized. METHODS: A cohort of gay men (n = 326) and a cohort of the general adult population (n = 295) were enrolled in this study. Binding antibodies responses against MPXV/vaccinia and neutralizing antibody responses against vaccinia virus (Tiantan strain) were measured. The antibody responses of these two cohorts were then compared, as well as the responses of individuals born before and in/after 1981 (when the smallpox vaccination ceased in China). Finally, the correlation between the anti-MPXV antibody responses and the anti-vaccinia antibody responses, and the associations between preexisting anti-orthopoxvirus antibody responses and the diagnosed sexually transmitted infections (STIs) in the MSM cohort were analyzed separately. RESULTS: Our data showed that binding antibodies against MPXV H3, A29, A35, E8, B6, M1 proteins and vaccinia whole-virus lysate could be detected in individuals born both before and in/after 1981, of which the prevalence of anti-vaccinia binding antibodies was significantly higher among individuals born before 1981 in the general population cohort. Moreover, we unexpectedly found that the positive rates of binding antibody responses against MPXV H3, A29, A35, E8 and M1 proteins were significantly lower among individuals of the MSM cohort born in/after 1981, but the positive rates of anti-MPXV B6 and anti-vaccinia neutralizing antibody responses were significantly higher among these individuals compared to those of age-matched participants in the general population cohort. Additionally, we demonstrated that the positive and negative rates of anti-MPXV antibody responses were associated with the anti-vaccinia antibody responses among individuals born before 1981 in the general population cohort, but no significant association was observed among individuals born in/after 1981 in both cohorts. The positive rates of both the binding and the neutralizing antibody responses were comparable between individuals with and without diagnosed STIs in the MSM cohort. CONCLUSIONS: Anti-MPXV and anti-vaccinia antibodies could be readily detected in an MSM cohort and a general population cohort. And a higher level of anti-vaccinia neutralizing antibody responses was observed among individuals who did not get vaccinated against smallpox in the MSM cohort compared to age-matched individuals in the general population cohort.

DLGAP1-AS2 promotes human colorectal cancer progression through trans-activation of Myc.

Substantial evidence suggests that non-coding RNA plays a vital role in human cancer, especially long non-coding RNA (lncRNA) with a length greater than 200nt. Herein, we found a lncRNA facilitating human colorectal cancer (CRC) progression. DLGAP1-AS2 was significantly increased in CRC tissues and cell lines. Knockdown of DLGAP1-AS2 inhibited CRC cell proliferation, migration, invasion in vitro, and tumor growth in vivo. The subcellular localization of DLGAP1-AS2 was translocated from the cytoplasm of normal cells to the nucleus of CRC cells due to reduced levels of N6-methyladenosine (m6A) modification. Further, through the screening of a series of signal pathways, we found that Myc pathway was involved in the effect of DLGAP1-AS2. Silencing of DLGAP1-AS2 markedly reduced Myc mRNA and protein levels. Blockade of Myc effectively abolished the enhanced aggressive behaviors of CRC cells caused by DLGAP1-AS2 overexpression. Mechanistically, DLGAP1-AS2 directly bound CTCF, a well-known transcriptional repressor of Myc, resulting in reduced binding of CTCF on Myc promoter and activating Myc transcription. The second hairpin structure of DLGAP1-AS2 was critical for the interaction between DLGAP1-AS2 and CTCF in the nucleus. Taken together, our study reveals the oncogenic regulatory axis of DLGAP1-AS2/CTCF/Myc in CRC, implying a promising targeted therapy for clinical application.

Circular RNA hsa_circ_0001178 facilitates the invasion and metastasis of colorectal cancer through upregulating ZEB1 via sponging multiple miRNAs.

Metastasis is the main cause of increasing cancer morbidity and mortality. However, the underlying mechanism of cancer metastasis remains largely unknown. In the present study, we identified one circular RNA (circRNA) closely related to the metastasis of colorectal cancer (CRC), namely hsa_circ_0001178. CRC patients with high hsa_circ_0001178 were more prone to have metastatic clinical features, advanced TNM stage and adverse prognosis. Stable knockdown of hsa_circ_0001178 significantly weakened CRC cell migratory and invasive capabilities in vitro as well as lung and liver metastases in vivo. Mechanistic study revealed that hsa_circ_0001178 acted as a competing endogenous RNA (ceRNA) for miR-382/587/616 to upregulate ZEB1 (a key trigger of epithelial-to-mesenchymal transition), thereby promoting CRC metastatic dissemination. Of note, ZEB1 could also increase hsa_circ_0001178 expression via physically binding to hsa_circ_0001178 promoter region. Collectively, our data uncover the crucial role of hsa_circ_0001178 in CRC metastasis, and targeted therapy based on this positive feedback ceRNA axis may be a promising treatment for metastatic CRC patients.

The role of IDO, IL-10, and TGF-ß in the HCV-associated chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma.

Indoleamine-2,3-dioxygenase (IDO) is an enzyme that catalyzes tryptophan to kynurenine and studies have revealed that IDO play a vital role in regulation of liver immunity and inflammation activities. This study investigated the association between plasma IDO and disease severity and the possible marker role of IDO in the inflammatory process of hepatitis C. In this study, 80 individuals with HCV infection were retrospectively selected. Plasma levels of IDO, IL-10, and TGF-ß were assayed by ELISA. Clinical characteristics of patients, including the levels of ALT, AST, and total bilirubin (TBil) were collected from clinical databases. HCV-related liver cirrhosis (HC-Cirr) and HCV-related Hepatocellular carcinoma (HCV-HCC) had significantly high plasma levels of IDO compared to other patient groups and healthy controls. Plasma IL-10 level were significantly greater in all chronic liver disease groups and with respect to TGF-ß, the level was high in all the selected patients with HCV infection compare with controls. Moreover, HCV-HCC patients showed highest values for both IL-10 and TGF-ß, with significant difference compared with other groups. In addition, plasma IDO was positively correlated with TGF-ß among all patients with HCV infection (r = 0.4509, P < 0.0001), with IL-10 in CHC patients (r = 0.4787, P = 0.0047), with TBil in HCV-Cirr patients (r = 0.4671; P = 0.0093). High level of IDO and TGF-ß is associated with hepatocyte necrosis and intrahepatic inflammation, and may be used as an index of disease progression for patients with chronic HCV infection.

Determinant roles of gender and age on SII, PLR, NLR, LMR and MLR and their reference intervals defining in Henan, China: A posteriori and big-data-based.

OBJECTIVES: By now, there are few data of the reference intervals (RIs) of SII, PLR, NLR, LMR and MLR. We aimed to establish RIs of SII, PLR, NLR, LMR and MLR for healthy persons. METHODS: A retrospective analysis on a cohort of ostensibly healthy, aged no <18 years old physical examinees who took health examination from January to December in 2013 was conducted to explore influences of age and gender on SII, PLR, NLR, LMR and MLR and to establish their RIs. And another cohort of 450 persons in our hospital from January to July in 2016 is included for validations of RIs. RESULTS: NLR, LMR and MLR were significantly different between gender groups (P=.010; P<.001; P<.001, separately), while SII and PLR were not (P=.137; P=.267, separately). While SII was not changed much between age groups (P=.842), PLR, NLR, LMR and MLR were significantly different (all with P<.001). RIs of SII, PLR, NLR, LMR and MLR were: SII: [161,701]; PLR: 18-65 year-old: [61,179]/>65 year-old: [55,179]; NLR: 18-65 year-old male: [0.90,2.94]/18-65 year-old female: [0.85,3.06]/>65 year-old male: [0.95,3.57]/aged >65 year-old female: [0.83,3.30]; LMR: 18-65 year-old male: [2.50,7.50]/18-65 year-old female: [2.75,8.50]/>65 year-old male: [2.16,7.41]/>65 year-old female: [2.40,8.33]; MLR: 18-65 year-old male: [0.12,0.35]/18-65 year-old female: [0.10,0.32]/>65 year-old male: [0.12,0.41]/>65 year-old male: [0.11,0.33]. CONCLUSIONS: RIs of SII, PLR, NLR, LMR and MLR of people in central China were established and validated. It will benefit experimental design of the related studies and lead to better standardizations of SII, PLR, NLR, LMR and MLR for their clinical applications.

The upregulation of LAG-3 on T cells defines a subpopulation with functional exhaustion and correlates with disease progression in HIV-infected subjects.

T cells develop functional defects during HIV-1 infection, partially due to the upregulation of inhibitory receptors such as programmed death-1 (PD-1) and CTLA-4. However, the role of lymphocyte activation gene-3 (LAG-3; CD223), also known as an inhibitory receptor, in HIV infection remains to be determined. In this study, we revealed that LAG-3 on T cells delivers an inhibitory signal to downregulate T cell functionality, thereby playing an immunoregulatory role during persistent HIV-1 infection. We observed that HIV-1 infection results in a significant increase in LAG-3 expression in both the peripheral blood and the lymph nodes. The upregulation of LAG-3 is dramatically manifested on both CD4(+) and CD8(+) T cells and is correlated with disease progression. As expected, prolonged antiretroviral therapy reduces the expression of LAG-3 on both CD4(+) and CD8(+) T cells. The ex vivo blockade of LAG-3 significantly augments HIV-specific CD4(+) and CD8(+) T cell responses, whereas the overexpression of LAG-3 in T cells or the stimulation of LAG-3 on T cells leads to the reduction of T cell responses. Furthermore, most LAG-3 and PD-1 are expressed in different T cell subsets. Taken together, these data demonstrate that the LAG-3/MHC class II pathway plays an immunoregulatory role, thereby providing an important target for enhancing immune reconstitution in HIV-infected patients. Additionally, the LAG-3/MHC class II pathway may synergize with PD-1/PD ligand to enhance T cell-mediated immune responses.

Diagnostic value of autoantibodies combined detection for rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic, inflammatory and autoimmune disease, there are many autoantibodies produced during disease progression in the patients' serum, and this work is to select a best detection scheme for RA diagnosis. METHODS: Autoantibody levels including rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP), mutated citrullinated vimentin (MCV), anti-keratin antibodies(AKA), anti-perinuclear factor (APF), and Ig heavy chain binding protein (BIP), were measured, and the sensitivity, specificity, predictive values, accuracy, and Youden's index of different combining forms were all calculated in RA patients, disease, and healthy control group. The differences in the positive rates of the three groups were compared between any two of them. RESULTS: Generally speaking, the sensitivity of the autoantibodies detected in parallel combination was higher than that in tandem, which was more specific. The sensitivity of anti-MCV and RF calculated in parallel (87.61%) was obviously better than that of anyone autoantibody (P<.05), and only increased slightly even if more autoantibodies were tested in parallel (P>.05). The specificity of anti-CCP and BIP measured in tandem (95.92%) was obviously higher than that of anyone autoantibody (P<.05). While increasing the detected number of autoantibody from two kinds to three or more, the specificity was improved insignificantly (P>.05). CONCLUSION: Anti-BIP and CCP antibodies detected in tandem combination can obtain higher specificity, and have good clinical value for the differential diagnosis of RA.

A biphenotypic lymphocyte subset displays both T- and B-cell functionalities.

T cell/B cell mixed phenotypic lymphocytes have been observed in different disease contexts, yet their presence and function in physiological conditions remain elusive. Here, we provide evidence for the existence of a lymphocyte subset endogenously expressing both T- and B-cell lineage markers in mice. The majority of these T/B phenotypic lymphocytes (CD3+CD19+) show an origin of pro/pre B cells and distribute widely in mouse bone marrow, lymph nodes, spleen, and peripheral blood. Functional assays show that these biphenotypic lymphocytes can be activated through stimulating TCR or BCR signaling pathways. Moreover, we show that these cells actively participate both the humoral and cellular immune responses elicited by vaccination. Compared to conventional T cells, these biphenotypic lymphocytes can secrete a higher level of IL-2 but a lower level of TNF-α upon antigen specific stimulation. An equivalent lymphocyte subset is found in freshly isolated human PBMCs and exhibits similar functionality, albeit at a lower frequency than in mice.

Conjugated Phosphonic Acids Enable Robust Hole Transport Layers for Efficient and Intrinsically Stable Perovskite Solar Cells.

High efficiency and long-term stability are the prerequisites for the commercialization of perovskite solar cells (PSCs). However, inadequate and non-uniform doping of hole transport layers (HTLs) still limits the efficiency improvements, while the intrinsic instability of HTLs caused by ion migration and accumulation is difficult to be addressed by external encapsulation. Here it is shown that the addition of a conjugated phosphonic acid (CPA) to the Spiro-OMeTAD benchmark HTL can greatly enhance the device efficiency and intrinsic stability. Featuring an optimal diprotic-acid structure, indolo(3,2-b)carbazole-5,11-diylbis(butane-4,1-diyl) bis(phosphonic acid) (BCZ) is developed to promote morphological uniformity and mitigate ion migration across both perovskite/HTL and HTL/Ag interfaces, leading to superior charge conductivity, reinforced ion immobilization, and remarkable film stability. The dramatically improved interfacial charge collection endows BCZ-based n-i-p PSCs with a champion power conversion efficiency of 24.51%. More encouragingly, the BCZ-based devices demonstrate remarkable stability under harsh environmental conditions by retaining 90% of initial efficiency after 3000 h in air storage. This work paves the way for further developing robust organic HTLs for optoelectronic devices.

In situ Blending For Co-Deposition of Electron Transport and Perovskite Layers Enables Over 24% Efficiency Stable Inverted Solar Cells.

Simplifying the manufacturing processes of multilayered high-performance perovskite solar cells (PSCs) is yet of vital importance for their cost-effective production. Herein, an in situ blending strategy is presented for co-deposition of electron transport layer (ETL) and perovskite absorber by incorporating (3-(7-butyl-1,3,6,8-tetraoxo-3,6,7,8-tetrahydrobenzo- [lmn][3,8]phenanthrolin-2(1H)-yl)propyl)phosphonic acid (NDP) into the perovskite precursor solutions. The phosphonic acid-like anchoring group coupled with its large molecular size drives the migration of NDP toward indium tin oxide (ITO) surface to form a distinct ETL during perovskite film forming. This strategy circumvents the critical wetting issue and simultaneously improves the interfacial charge collection efficiencies. Consequently, n-i-p PSCs based on in situ blended NDP achieve a champion power conversion efficiency (PCE) of 24.01%, which is one of the highest values for PSCs using organic ETLs. This performance is notably higher than that of ETL-free (21.19%) and independently spin-coated (21.42%) counterparts. More encouragingly, the in situ blending strategy dramatically enhances the device stability under harsh conditions by retaining over 90% of initial efficiencies after 250 h in 100 °C or 65% humidity storage. Moreover, this strategy is universally adaptable to various perovskite compositions, device architectures, and electron transport materials (ETMs), showing great potential for applications in diverse optoelectronic devices.

Fluorinated Naphthalene Diimides as Buried Electron Transport Materials Achieve Over 23% Efficient Perovskite Solar Cells.

Naphthalene diimides (NDI) are widely serving as the skeleton to construct electron transport materials (ETMs) for optoelectronic devices. However, most of the reported NDI-based ETMs suffer from poor interfaces with the perovskite which deteriorates the carrier extraction and device stability. Here, a representative design concept for editing the peripheral groups of NDI molecules to achieve multifunctional properties is introduced. The resulting molecule 2,7-bis(2,2,3,3,4,4,4-heptafluorobutyl)benzo[lmn][3,8]phenanthroline-1,3,6,8(2H,7H)-tetraone (NDI-C4F) incorporated with hydrophobic fluorine units contributes to the prevention of excessive molecular aggregation, the improvement of surface wettability and the formation of strong chemical coordination with perovskite precursors. All these features favor retarding the perovskite crystallization and achieving superior buried interfaces, which subsequently promote charge collection and improve the structural compatibility between perovskite and ETMs. The corresponding PSCs based on low-temperature processed NDI-C4F yield a record efficiency of 23.21%, which is the highest reported value for organic ETMs in n-i-p PSCs. More encouragingly, the unencapsulated devices with NDI-C4F demonstrate extraordinary stability by retaining over 90% of their initial PCEs after 2600 h in air. This work provides an alternative molecular strategy to engineer the buried interfaces and can trigger further development of organic ETMs toward reliable PSCs.

Dynamic self-assembly of small molecules enables the spontaneous fabrication of hole conductors at perovskite/electrode interfaces for over 22% stable inverted perovskite solar cells.

The bottom hole transport layers (HTLs) are of paramount importance in determining both the efficiency and stability of inverted perovskite solar cells (PSCs), however, their surface nature and properties strongly interfere with the upper perovskite crystallization kinetics and also influence interfacial carrier dynamics. In this work, we strategically develop a simple, facile and spontaneous fabrication method of the HTL at the perovskite/electrode interface by dynamic self-assembly (DSA) of small molecules during perovskite crystallization. Different from the traditional layer-by-layer approach, this DSA strategy involves a bilateral movement of self-assembled molecules (SAMs) from perovskite solution, realizing simultaneous fabrication of the HTL and perovskite surface passivation. We design a multifunctional molecule, (4-(7H-benzo[c]carbazol-7-yl)butyl)phosphonic acid (BCB-C4PA), for the DSA process, to optimize both self-assembly ability and interfacial energy alignment. Benefitting from this unconventional DSA approach and BCB-C4PA, a champion PCE of 22.2% is achieved along with remarkable long-term environmental stability for over 2750 h, which is among the highest reported efficiencies for SAM-based PSCs. This investigation provides a creative, unique and effective molecular approach for preparing reliable charge transport layers, opening up new avenues for the further development of efficient interfacial contacts for PSCs.

The impacts of vaccination status and host factors during early infection on SARS-CoV-2 persistence:a retrospective single-center cohort study.

BACKGROUND: Viral persistence is a crucial factor that influences the transmissibility of SARS-CoV-2. However, the impacts of vaccination and physiological variables on viral persistence have not been adequately clarified. METHODS: We collected the clinical records of 377 COVID-19 patients, which contained unvaccinated patients and patients received two doses of an inactivated vaccine or an mRNA vaccine. The impacts of vaccination on disease severity and viral persistence and the correlations between 49 laboratory variables and viral persistence were analyzed separately. Finally, we established a multivariate regression model to predict the persistence of viral RNA. RESULTS: Both inactivated and mRNA vaccines significantly reduced the rate of moderate cases, while the vaccine related shortening of viral RNA persistence was only observed in moderate patients. Correlation analysis showed that 10 significant laboratory variables were shared by the unvaccinated mild patients and mild patients inoculated with an inactivated vaccine, but not by the mild patients inoculated with an mRNA vaccine. A multivariate regression model established based on the variables correlating with viral persistence in unvaccinated mild patients could predict the persistence of viral RNA for all patients except three moderate patients inoculated with an mRNA vaccine. CONCLUSION: Vaccination contributed limitedly to the clearance of viral RNA in COVID-19 patients. While, laboratory variables in early infection could predict the persistence of viral RNA.

Successive Site Translocating Inoculation Improved T Cell Responses Elicited by a DNA Vaccine Encoding SARS-CoV-2 S Protein.

A variety of methods have been explored to increase delivery efficiencies for DNA vaccine. However, the immunogenicity of DNA vaccines has not been satisfactorily improved. Unlike most of the previous attempts, we provided evidence suggesting that changing the injection site successively (successively site-translocated inoculation, SSTI) could significantly enhance the immunogenicity of DNA vaccines in a previous study. To simplify the strategy and to evaluate its impact on candidate SARS-CoV-2 vaccines, we immunized mice with either a SARS-CoV-2 spike-based DNA vaccine or a spike protein subunit vaccine via three different inoculation strategies. Our data demonstrated that S protein specific antibody responses elicited by the DNA vaccine or the protein subunit vaccine showed no significant difference among different inoculation strategies. Of interest, compared with the conventional site fixed inoculation (SFI), both successive site-translocating inoculation (SSTI) and the simplified translocating inoculation (STI) strategy improved specific T cell responses elicited by the DNA vaccine. More specifically, the SSTI strategy significantly improved both the monofunctional (IFN-γ+IL-2-TNF-α-CD8+) and the multifunctional (IFN-γ+IL-2-TNF-α+CD8+, IFN-γ+IL-2-TNF-α+CD4+, IFN-γ+IL-2+TNF-α+CD4+) T cell responses, while the simplified translocating inoculation (STI) strategy significantly improved the multifunctional CD8+ (IFN-γ+IL-2-TNF-α+CD8+, IFN-γ+IL-2+TNF-α+CD8+) and CD4+ (IFN-γ+IL-2-TNF-α+CD4+, IFN-γ+IL-2+TNF-α+CD4+) T cell responses. The current study confirmed that changing the site of intra muscular injection can significantly improve the immunogenicity of DNA vaccines.

Omicron Booster in Ancestral Strain Vaccinated Mice Augments Protective Immunities Against Both Delta and Omicron Variants.

A booster vaccination is called for constraining the evolving epidemic of SARS-CoV-2. However, the necessity of a new COVID-19 vaccine is currently unclear. To compare the effect of an Omicron-matched S DNA vaccine and an ancestral S DNA vaccine in boosting cross-reactive immunities, we firstly immunized mice with two-dose of a DNA vaccine encoding the spike protein of the ancestral Wuhan strain. Then the mice were boosted with DNA vaccines encoding spike proteins of either the Wuhan strain or the Omicron variant. Specific antibody and T cell responses were measured at 4 weeks post boost. Our data showed that the Omicron-matched vaccine efficiently boosted RBD binding antibody and neutralizing antibody responses against both the Delta and the Omicron variants. Of note, antibody responses against the Omicron variant elicited by the Omicron-matched vaccine were much stronger than those induced by the ancestral S DNA vaccine. Meanwhile, CD8+ T cell responses against both the ancestral Wuhan strain and the Omicron strain also tended to be higher in mice boosted by the Omicron-matched vaccine than those in mice boosted with the ancestral S DNA vaccine, albeit no significant difference was observed. Our findings suggest that an Omicron-matched vaccine is preferred for boosting cross-protective immunities.

Immunogenicity of an inactivated SARS-CoV-2 vaccine in people living with HIV-1: a non-randomized cohort study.

BACKGROUND: Inactivated COVID-19 vaccines are safe and effective in the general population with intact immunity. However, their safety and immunogenicity have not been demonstrated in people living with HIV (PLWH). METHODS: 42 HIV-1 infected individuals who were stable on combination antiretroviral therapy (cART) and 28 healthy individuals were enrolled in this open-label two-arm non-randomized study at Hubei Provincial Center for Disease Control and Prevention, China. Two doses of an inactivated COVID-19 vaccine (BBIBP-CorV) were given on April 22, 2021 and May 25, 2021, respectively. The reactogenicity of the vaccine were evaluated by observing clinical adverse events and solicited local and systemic reactions. Humoral responses were measured by anti-spike IgG ELISA and surrogate neutralization assays. Cell-mediated immune responses and vaccine induced T cell activation were measured by flow cytometry. FINDINGS: All the HIV-1 infected participants had a CD4+ T cell count >200 cells/µL both at baseline (659·0 ± 221·9 cells/µL) and 4 weeks after vaccination (476·9 ± 150·8 cells/µL). No solicited adverse reaction was observed among all participants. Similar binding antibody, neutralizing antibody and S protein specific T cell responses were elicited in PLWH and healthy individuals. PLWH with low baseline CD4+/CD8+ T cell ratios (<0·6) generated lower antibody responses after vaccination than PLWH with medium (0·6∼1·0) or high (≥1·0) baseline CD4+/CD8+ T cell ratios (P<0·01). The CD3+, CD4+ and CD8+ T cell counts of PLWH decreased significantly after vaccination (P<0·0001), but it did not lead to any adverse clinical manifestation. Moreover, we found that the general HIV-1 viral load among the PLWH cohort decreased significantly after vaccination (P=0·0192). The alteration of HIV-1 viral load was not significantly associated with the vaccine induced CD4+ T cell activation (P>0·2). INTERPRETATION: Our data demonstrated that the inactivated SARS-CoV-2 vaccine was safe, immunogenic in PLWH who are stable on cART with suppressed viral load and CD4+ T cell count > 200 cells/µL. However, the persistence of the vaccine-induced immunities in PLWH need to be further investigated.

Preexisting antibodies targeting SARS-CoV-2 S2 cross-react with commensal gut bacteria and impact COVID-19 vaccine induced immunity.

The origins of preexisting SARS-CoV-2 cross-reactive antibodies and their potential impacts on vaccine efficacy have not been fully clarified. In this study, we demonstrated that S2 was the prevailing target of the preexisting S protein cross-reactive antibodies in both healthy human and SPF mice. A dominant antibody epitope was identified on the connector domain of S2 (1147-SFKEELDKYFKNHT-1160, P144), which could be recognized by preexisting antibodies in both human and mouse. Through metagenomic sequencing and fecal bacteria transplant, we demonstrated that the generation of S2 cross-reactive antibodies was associated with commensal gut bacteria. Furthermore, six P144 reactive monoclonal antibodies were isolated from naïve SPF mice and were proven to cross-react with commensal gut bacteria collected from both human and mouse. A variety of cross-reactive microbial proteins were identified using LC-MS, of which E. coli derived HSP60 and HSP70 proteins were confirmed to be able to bind to one of the isolated monoclonal antibodies. Mice with high levels of preexisting S2 cross-reactive antibodies mounted higher S protein specific binding antibodies, especially against S2, after being immunized with a SARS-CoV-2 S DNA vaccine. Similarly, we found that levels of preexisting S2 and P144-specific antibodies correlated positively with RBD binding antibody titers after two doses of inactivated SARS-CoV-2 vaccination in human. Collectively, our study revealed an alternative origin of preexisting S2-targeted antibodies and disclosed a previously neglected aspect of the impact of gut microbiota on host anti-SARS-CoV-2 immunity.